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Original Articles
Impact of TTF-1 Expression on the Prognostic Prediction of Patients with NSCLC with PD-L1 Expression Levels of 1% to 49%, Treated with Chemotherapy vs Chemoimmunotherapy: A Multicenter, Retrospective Study
Naoya Nishioka, Tae Hata, Tadaaki Yamada, Yasuhiro Goto, Akihiko Amano, Yoshiki Negi, Satoshi Watanabe, Naoki Furuya, Tomohiro Oba, Tatsuki Ikoma, Akira Nakao, Keiko Tanimura, Hirokazu Taniguchi, Akihiro Yoshimura, Tomoya Fukui, Daiki Murata, Kyoichi Kaira, Shinsuke Shiotsu, Makoto Hibino, Asuka Okada, Yusuke Chihara, Hayato Kawachi, Takashi Kijima, Koichi Takayama
Received August 7, 2024  Accepted October 24, 2024  Published online October 25, 2024  
DOI: https://doi.org/10.4143/crt.2024.748    [Accepted]
AbstractAbstract PDF
Purpose
Thyroid transcription factor 1 (TTF-1) expression is a useful predictor of treatment efficacy in advanced non-squamous non-small-cell lung cancer (NSCLC). This study aimed to evaluate whether TTF-1 could predict the effectiveness of chemotherapy versus chemoimmunotherapy in patients with non-squamous NSCLC with programmed death ligand-1 (PD-L1) expression between 1% and 49%.
Materials and Methods
We conducted a retrospective study of patients with NSCLC who were treated with chemotherapy or chemoimmunotherapy between March 2016 and May 2023. The patients had histologically confirmed NSCLC, stage III-IV or postoperative recurrence, TTF-1 measurements, and PD-L1 expression levels between 1% and 49%. Clinical data were analyzed to evaluate the effect of TTF-1 expression on treatment efficacy.
Results
This study included 283 of 624 patients. TTF-1-positive patients showed longer progression-free survival (PFS) and overall survival (OS) (PFS: 6.4 months [95% confidence interval (CI): 5.0−9.4] vs 4.1 months [95% CI: 2.7−6.1], p=0.03, OS: 17.9 months [95% CI: 15.2−28.1] vs 9.4 months [95% CI: 6.3−17.0], p<0.01) in the chemotherapy cohorts (n=93). In the chemoimmunotherapy cohort (n=190), there was no significant difference in PFS and OS between TTF-1-positive and negative groups (PFS: 7.6 months [95% CI: 6.4−11.0] vs 6.0 months [95% CI: 3.6−12.6], p=0.59, OS: 25.0 months [95% CI: 18.0−49.2] vs 21.3 months [95% CI: 9.8−28.8], p=0.09).
Conclusion
In patients with NSCLC with PD-L1 expression between 1% and 49%, TTF-1 expression was a predictor of chemotherapeutic, but not chemoimmunotherapeutic, efficacy.
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Lung and Thoracic cancer
Association of TP53 Mutation Status and Sex with Clinical Outcome in Non–Small Cell Lung Cancer Treated with Immune Checkpoint Inhibitors: A Retrospective Cohort Study
Songji Choi, Se Hyun Kim, Sejoon Lee, Jeongmin Seo, Minsu Kang, Eun Hee Jung, Sang-A Kim, Koung Jin Suh, Ji Yun Lee, Ji-Won Kim, Jin Won Kim, Jeong-Ok Lee, Yu Jung Kim, Keun-Wook Lee, Jee Hyun Kim, Soo-Mee Bang, Jong Seok Lee
Cancer Res Treat. 2025;57(1):70-82.   Published online August 7, 2024
DOI: https://doi.org/10.4143/crt.2024.046
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Some studies suggest that TP53 mutations are associated with the response to immune checkpoint inhibitors (ICI) in patients with non–small cell lung cancer (NSCLC) and also contribute to sex disparities in several cancers. Thus, we hypothesized that TP53 mutations might serve as sex-dependent genomic biomarkers of ICI treatment response in patients with NSCLC.
Materials and Methods
Clinical data of 100 patients with metastatic NSCLC treated with ICI monotherapy at Seoul National University Bundang Hospital (SNUBH) were retrospectively reviewed. Genomic and clinical datasets of The Cancer Genome Atlas and an ICI-treated lung cancer cohort (cBioPortal) were also analyzed.
Results
In SNUBH cohort, no statistically significant difference was observed in the median progression-free survival (PFS) according to TP53 mutation status (p=0.930); however, female patients with TP53 mutations (MT) had a significantly prolonged median PFS compared to wild-type (WT) (6.1 months in TP53 MT vs. 2.6 months in TP53 WT; p=0.021). Programmed death-ligand 1 (PD-L1) high (≥ 50%) expression was significantly enriched in female patients with TP53 MT (p=0.005). The analysis from publicly available dataset also revealed that females with NSCLC with TP53 MT showed significantly longer PFS than those with TP53 WT (p < 0.001). In The Cancer Genome Atlas analysis, expression of immune-related genes, and tumor mutation burden score in TP53 MT females were higher than in males without TP53 MT.
Conclusion
Female patients with NSCLC with TP53 mutations had high PD-L1 expression and showed favorable clinical outcomes following ICI therapy, suggesting a need for further research to explore the role of TP53 mutations for sex disparities in response to ICI therapy.
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Association of Immune-Related Adverse Events and the Efficacy of Anti–PD-(L)1 Monotherapy in Non–Small Cell Lung Cancer: Adjusting for Immortal-Time Bias
Ying Yu, Ning Chen, Sizhe Yu, Wanji Shen, Wanchen Zhai, Hui Li, Yun Fan
Cancer Res Treat. 2024;56(3):751-764.   Published online January 2, 2024
DOI: https://doi.org/10.4143/crt.2023.1118
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
The association between immune-related adverse events (irAEs) and survival outcomes in non–small cell lung cancer (NSCLC) patients treated with programmed death-(ligand) 1 [PD-(L)1] inhibitors remains controversial, partly due to variations in dealing with immortal-time bias (ITB).
Materials and Methods
We retrospectively enrolled 425 advanced NSCLC patients who received anti–PD-(L)1 monotherapy between January 2016 and June 2021, stratifying them into irAE (n=127) and non-irAE (n=298) groups. The primary endpoint was to assess the impact of irAEs on progression-free survival (PFS) and overall survival (OS). Landmark (2-, 3-, 6-, and 9-month) and time-dependent Cox analyses were performed to eliminate ITB.
Results
With a median follow-up of 38.8 months, the occurrence of overall irAEs was significantly associated with superior PFS (11.2 vs. 3.4 months, p < 0.001) and OS (31.4 vs. 14.0 months, p < 0.001), which persisted in landmark and time-dependent Cox analyses. For the main organ-specific irAEs, skin, thyroid, and hepatic irAEs, respectively, showed significantly improved survival compared to the non-irAE group, whereas pneumonitis did not. Single-organ irAEs had the best outcomes compared with multi-organ or no irAE, which also held across subgroups of skin, thyroid, and hepatic irAEs. Moreover, severe grade irAEs and immunotherapy discontinuation had a detrimental effect on survival, systemic steroid therapy showed little effect, while immunotherapy resumption had tolerable safety and a trend of improved survival.
Conclusion
After adequately adjusting ITB, the occurrence of overall irAEs predicts for favorable efficacy of anti–PD-(L)1 monotherapy in NSCLC, with better outcomes observed in patients with skin, thyroid, or hepatic irAEs, particularly those with single-organ involvement.

Citations

Citations to this article as recorded by  
  • Management, biomarkers and prognosis in people developing endocrinopathies associated with immune checkpoint inhibitors
    Shintaro Iwama, Tomoko Kobayashi, Hiroshi Arima
    Nature Reviews Endocrinology.2025;[Epub]     CrossRef
  • Development of pituitary dysfunction and destructive thyroiditis is associated with better survival in non-small cell lung cancer patients treated with programmed cell death-1 inhibitors: a prospective study with immortal time bias correction
    Koji Suzuki, Tomoko Kobayashi, Tetsushi Izuchi, Koki Otake, Masahiko Ando, Tomoko Handa, Takashi Miyata, Mariko Sugiyama, Takeshi Onoue, Daisuke Hagiwara, Hidetaka Suga, Ryoichi Banno, Tetsunari Hase, Megumi Inoue, Makoto Ishii, Hiroshi Arima, Shintaro Iw
    Frontiers in Endocrinology.2024;[Epub]     CrossRef
  • Associations between Immune-related Adverse Events and Prognosis in Cancer Patients Receiving Immune Checkpoint Inhibitor Therapy
    Yusuke Inoue, Naoki Inui
    Internal Medicine.2024;[Epub]     CrossRef
  • The impact of immune-related adverse events on the outcome of advanced gastric cancer patients with immune checkpoint inhibitor treatment
    Tianhang Zhang, Haitao Lv, Jiasong Li, Shasha Zhang, Jingjing Zhang, Siqi Wang, Yingnan Wang, Zhanjun Guo
    Frontiers in Immunology.2024;[Epub]     CrossRef
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  • 5 Web of Science
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Breast cancer
PD-L1 (SP142) Expression in Primary and Recurrent/Metastatic Triple-Negative Breast Cancers and Its Clinicopathological Significance
Eun Kyung Han, Ji Won Woo, Koung Jin Suh, Se Hyun Kim, Jee Hyun Kim, So Yeon Park
Cancer Res Treat. 2024;56(2):557-566.   Published online December 12, 2023
DOI: https://doi.org/10.4143/crt.2023.1025
AbstractAbstract PDFPubReaderePub
Purpose
The programmed death-ligand 1 (PD-L1) SP142 assay identifies patients with triple-negative breast cancer (TNBC) who are most likely to respond to the anti–PD-L1 agent atezolizumab. We aimed to compare PD-L1 (SP142) expression between primary and recurrent/metastatic TNBCs and elucidate the clinicopathological features associated with its expression.
Materials and Methods
Primary and recurrent/metastatic TNBCs tested with PD-L1 (SP142) were collected, and clinicopathological information of these cases was obtained through a review of slides and medical records.
Results
PD-L1 (SP142) positivity was observed in 50.9% (144/283) of primary tumors and 37.8% (31/82) of recurrent/metastatic TNBCs with a significant difference. Recurrent or metastatic sites were associated with PD-L1 positivity, with high PD-L1 positivity in the lung, breast, and soft tissues, and low positivity in the bone, skin, liver, and brain. When comparing PD-L1 expression between primary and matched recurrent/metastatic TNBCs using 55 paired samples, 20 cases (36.4%) showed discordance; 10 cases revealed positive conversion, and another 10 cases revealed negative conversion during metastatic progression. In primary TNBCs, PD-L1 expression was associated with a higher histologic grade, lower T category, pushing border, and higher tumor-infiltrating lymphocyte infiltration. In survival analyses, PD-L1 positivity, especially high positivity, was found to be associated with favorable prognosis of patients.
Conclusion
PD-L1 (SP142) expression was lower in recurrent/metastatic TNBCs, and substantial cases showed discordance in its expression between primary and recurrent/metastatic sites, suggesting that multiple sites may need to be tested for PD-L1 (SP142) when considering atezolizumab therapy. PD-L1 (SP142)–positive TNBCs seems to be associated with favorable clinical outcomes.

Citations

Citations to this article as recorded by  
  • Solamargine inhibits gastric cancer progression via inactivation of STAT3/PD‑L1 signaling
    Xiongxiang Liu, Lin Song, Wen Liu, Bin Liu, Lang Liu, Yao Su
    Molecular Medicine Reports.2024;[Epub]     CrossRef
  • Prevalence of Programmed Death-Ligand 1 Positivity Using SP142 in Patients With Advanced Stage Triple-Negative Breast Cancer in Malaysia: A Cross-Sectional Study
    Pathmanathan Rajadurai, Ning Yi Yap, Seow Fan Chiew, Reena Rahayu Md Zin, Suria Hayati Md Pauzi, Aniqah Shamimi Binti Jaafar, Azyani Yahaya, Lai Meng Looi
    Journal of Breast Cancer.2024; 27(6): 362.     CrossRef
  • 3,385 View
  • 180 Download
  • 2 Web of Science
  • 2 Crossref
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Rare Cancer
Clinical Experience of Male Primary Choriocarcinoma at the Samsung Medical Center
Young Sok Ji, Se Hoon Park
Cancer Res Treat. 2021;53(3):874-880.   Published online December 7, 2020
DOI: https://doi.org/10.4143/crt.2020.1066
AbstractAbstract PDFPubReaderePub
Purpose
The objective of this study was to describe and analyze the clinicopathological features of primary choriocarcinoma (PCC) observed in male patients treated at the Samsung Medical Center between 1996 and 2020.
Materials and Methods
We reviewed the clinical records of 14 male patients with PCC retrospectively to assess their demographic, histological, and clinical characteristics at the time of diagnosis as well as identify the treatment outcomes.
Results
The median age of the patients was 33 years. The primary tumor site was the testicles in seven cases (50%), the mediastinum in six cases (43%), and the brain in one case (7%). The most common metastatic site was the lungs (79%), followed by the brain (43%). All patients with PCC received cytotoxic chemotherapy. Twelve patients had records of their response to cytotoxic chemotherapy; of these 12 patients, eight (8/12, 67%) achieved an objective response, and four (4/12, 33%) achieved stable disease response as the best response during chemotherapy.
Conclusion
It is known that most male PCC patients eventually develop resistance to cytotoxic chemotherapy and die. Factors such as poor response to chemotherapy, high disease burden, brain metastasis, and hemoptysis at the time of diagnosis are associated with shorter survival time in male PCC patients. Programmed death-1/programmed death-ligand 1 blockade therapy can be a salvage treatment for chemotherapy-resistant male PCC patients.

Citations

Citations to this article as recorded by  
  • Combination chemotherapy with sintilimab for treatment of a male patient with primary pulmonary choriocarcinoma: a case report and literature review
    Xiaojing Liang, Guoqing Xu, Jisong Zhang, Li Xu, Liangliang Dong, Xiaoyue Wang, Weidong Han, Enguo Chen
    Frontiers in Immunology.2025;[Epub]     CrossRef
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    Guimei Wang, Ronghui Li
    Oncologie.2024; 26(1): 167.     CrossRef
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  • Antineoplastics

    Reactions Weekly.2022; 1890(1): 41.     CrossRef
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    David Aguiar Bujanda, Daniel Pérez Cabrera, Laura Croissier Sánchez
    American Journal of Clinical Oncology.2022; 45(12): 493.     CrossRef
  • 7,128 View
  • 157 Download
  • 11 Web of Science
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A Radiosensitivity Gene Signature and PD-L1 Status Predict Clinical Outcome of Patients with Glioblastoma Multiforme in The Cancer Genome Atlas Dataset
Bum-Sup Jang, In Ah Kim
Cancer Res Treat. 2020;52(2):530-542.   Published online November 20, 2019
DOI: https://doi.org/10.4143/crt.2019.440
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Combination of radiotherapy and immune checkpoint blockade such as programmed death- 1 (PD-1) or programmed death-ligand 1 (PD-L1) blockade is being actively tested in clinical trial. We aimed to identify a subset of patients that could potentially benefit from this strategy using The Cancer Genome Atlas (TCGA) dataset for glioblastoma (GBM).
Materials and Methods
A total of 399 cases were clustered into radiosensitive versus radioresistant (RR) groups based on a radiosensitivity gene signature and were also stratified as PD-L1 high versus PD-L1 low groups by expression of CD274 mRNA. Differential and integrated analyses with expression and methylation data were performed. CIBERSORT was used to enumerate the immune repertoire that resulted from transcriptome profiles.
Results
We identified a subset of GBM, PD-L1-high-RR group which showed worse survival compared to others. In PD-L1-high-RR, differentially expressed genes (DEG) were highly enriched for immune response and mapped into activation of phosphoinositide 3-kinase–AKT and mitogen-activated protein kinase (MAPK) signaling pathways. Integration of DEG and differentially methylated region identified that the kinase MAP3K8-involved in T-cell receptor signaling was upregulated and BAI1, a factor which inhibits angiogenesis, was silenced. CIBERSORT showed that a higher infiltration of the immune repertoire, which included M2 macrophages and regulatory T cells.
Conclusion
Taken together, PD-L1-high-RR group could potentially benefit from radiotherapy combined with PD-1/PD-L1 blockade and angiogenesis inhibition.

Citations

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  • Clinical Biomarkers of Tumour Radiosensitivity and Predicting Benefit from Radiotherapy: A Systematic Review
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    Translational Oncology.2024; 44: 101955.     CrossRef
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    Ren Liu, Xiaojing Wang, Min Zhou, Jingfang Zhai, Jie Sun
    Biomedicine & Pharmacotherapy.2024; 180: 117491.     CrossRef
  • Bladder Cancer Treatments in the Age of Personalized Medicine: A Comprehensive Review of Potential Radiosensitivity Biomarkers
    Charbel Feghaly, Rafka Challita, Hanine Bou Hadir, Tala Mobayed, Tarek Al Bitar, Mohammad Harbi, Hala Ghorayeb, Rana El-Hassan, Larry Bodgi
    Biomarker Insights.2024;[Epub]     CrossRef
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    Zhiru Gao, Qian Zhao, Yiyue Xu, Linlin Wang
    Radiation Oncology.2023;[Epub]     CrossRef
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    Michael Zhang, Quan Zhou, Chinghsin Huang, Carmel T. Chan, Wei Wu, Gordon Li, Michael Lim, Sanjiv S. Gambhir, Heike E. Daldrup-Link
    Molecular Imaging and Biology.2022; 24(2): 280.     CrossRef
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    Bum-Sup Jang, In Ah Kim
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    Mi Sun Kim, Woong Sub Koom, Jae Ho Cho, Se-Young Kim, Ik Jae Lee
    Radiation Oncology.2022;[Epub]     CrossRef
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    Daniel Kreatsoulas, Chelsea Bolyard, Bill X. Wu, Hakan Cam, Pierre Giglio, Zihai Li
    Journal of Hematology & Oncology.2022;[Epub]     CrossRef
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    Maria Diaz Rosario, Harpreet Kaur, Erdal Tasci, Uma Shankavaram, Mary Sproull, Ying Zhuge, Kevin Camphausen, Andra Krauze
    Biomolecules.2022; 12(9): 1203.     CrossRef
  • Immunosuppression in Gliomas via PD-1/PD-L1 Axis and Adenosine Pathway
    Thamiris Becker Scheffel, Nathália Grave, Pedro Vargas, Fernando Mendonça Diz, Liliana Rockenbach, Fernanda Bueno Morrone
    Frontiers in Oncology.2021;[Epub]     CrossRef
  • The Combination of Radiotherapy With Immunotherapy and Potential Predictive Biomarkers for Treatment of Non-Small Cell Lung Cancer Patients
    Lu Meng, Jianfang Xu, Ying Ye, Yingying Wang, Shilan Luo, Xiaomei Gong
    Frontiers in Immunology.2021;[Epub]     CrossRef
  • Explore association of genes in PDL1/PD1 pathway to radiotherapy survival benefit based on interaction model strategy
    Junjie Shen, Jingfang Liu, Huijun Li, Lu Bai, Zixuan Du, Ruirui Geng, Jianping Cao, Peng Sun, Zaixiang Tang
    Radiation Oncology.2021;[Epub]     CrossRef
  • Combination of Radiosensitivity Gene Signature and PD-L1 Status Predicts Clinical Outcome of Patients With Locally Advanced Head and Neck Squamous Cell Carcinoma: A Study Based on The Cancer Genome Atlas Dataset
    Dongjun Dai, Yinglu Guo, Yongjie Shui, Jinfan Li, Biao Jiang, Qichun Wei
    Frontiers in Molecular Biosciences.2021;[Epub]     CrossRef
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    Li-Bo Liang, Xin-Yan Huang, He He, Ji-Yan Liu
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  • Gene signature based on B cell predicts clinical outcome of radiotherapy and immunotherapy for patients with lung adenocarcinoma
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    Cancer Medicine.2020; 9(24): 9581.     CrossRef
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  • 19 Web of Science
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Apatinib Combined with Local Irradiation Leads to Systemic Tumor Control via Reversal of Immunosuppressive Tumor Microenvironment in Lung Cancer
Li-jun Liang, Chen-xi Hu, Yi-xuan Wen, Xiao-wei Geng, Ting Chen, Guo-qing Gu, Lei Wang, You-you Xia, Yong Liu, Jia-yan Fei, Jie Dong, Feng-hua Zhao, Yiliyar Ahongjiang, Kai-yuan Hui, Xiao-dong Jiang
Cancer Res Treat. 2020;52(2):406-418.   Published online September 3, 2019
DOI: https://doi.org/10.4143/crt.2019.296
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
This study aimed to investigate the potential systemic antitumor effects of stereotactic ablative radiotherapy (SABR) and apatinib (a novel vascular endothelial growth factor receptor 2 inhibitor) via reversing the immunosuppressive tumor microenvironment for lung carcinoma.
Materials and Methods
Lewis lung cancer cells were injected into C57BL/6 mice in the left hindlimb (primary tumor; irradiated) and in the right flank (secondary tumor; nonirradiated). When both tumors grew to the touchable size, mice were randomly divided into eight treatment groups. These groups received normal saline or three distinct doses of apatinib (50 mg/kg, 150 mg/kg, and 200 mg/kg) daily for 7 days, in combination with a single dose of 15 Gy radiotherapy or not to the primary tumor. The further tumor growth/regression of mice were followed and observed.
Results
For the single 15 Gy modality, tumor growth delay could only be observed at the primary tumor. When combining SABR and apatinib 200 mg/kg, significant retardation of both primary and secondary tumor growth could be observed, indicated an abscopal effect was induced. Mechanism analysis suggested that programmed death-ligand 1 expression increased with SABR was counteract by additional apatinib therapy. Furthermore, when apatinib was combined with SABR, the composition of immune cells could be changed. More importantly, this two-pronged approach evoked tumor antigen–specific immune responses and the mice were resistant to another tumor rechallenge, finally, long-term survival was improved.
Conclusion
Our results suggested that the tumor microenvironment could be managed with apatinib, which was effective in eliciting an abscopal effect induced by SABR.

Citations

Citations to this article as recorded by  
  • Comparison of Efficacy and Safety of Different Second-line Therapies for Patients With Advanced Thymic Carcinoma
    K. Shao, Y. Hao, M. Xu, Z. Shi, G. Lin, C. Xu, Y. Zhang, Z. Song
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    Hailong Sheng, Yongyi Luo, Liting Zhong, Zhiyi Wang, Zhichao Sun, Xinna Gao, Xinrong He, Zhenru Zhu, Dehua Wu, Jingyuan Sun, Chuanhui Cao
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    Karl-Göran Tranberg
    Frontiers in Oncology.2021;[Epub]     CrossRef
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    Lin Li, Yuexian Li, Huawei Zou
    PeerJ.2021; 9: e12356.     CrossRef
  • 9,753 View
  • 361 Download
  • 7 Web of Science
  • 7 Crossref
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Therapeutic Co-targeting of WEE1 and ATM Downregulates PD-L1 Expression in Pancreatic Cancer
Mei Hua Jin, Ah-Rong Nam, Ji Eun Park, Ju-Hee Bang, Yung-Jue Bang, Do-Youn Oh
Cancer Res Treat. 2020;52(1):149-166.   Published online June 25, 2019
DOI: https://doi.org/10.4143/crt.2019.183
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Pancreatic cancer (PC) is one of the most lethal cancers worldwide, but there are currently no effective treatments. The DNA damage response (DDR) is under investigation for the development of novel anti-cancer drugs. Since DNA repair pathway alterations have been found frequently in PC, the purpose of this study was to test the DDR-targeting strategy in PC using WEE1 and ATM inhibitors.
Materials and Methods
We performed in vitro experiments using a total of ten human PC cell lines to evaluate antitumor effect of AZD1775 (WEE1 inhibitor) alone or combination with AZD0156 (ATM inhibitor). We established Capan-1–mouse model for in vivo experiments to confirm our findings.
Results
In our research, we found that WEE1 inhibitor (AZD1775) as single agent showed anti-tumor effects in PC cells, however, targeting WEE1 upregulated p-ATM level. Here, we observed that co-targeting of WEE1 and ATM acted synergistically to reduce cell proliferation and migration, and to induce DNA damage in vitro. Notably, inhibition of WEE1 or WEE1/ATM downregulated programmed cell death ligand 1 expression by blocking glycogen synthase kinase-3β serine 9 phosphorylation and decrease of CMTM6 expression. In Capan-1 mouse xenograft model, AZD1775 plus AZD0156 (ATM inhibitor) treatment reduced tumor growth and downregulated tumor expression of programmed cell death ligand 1, CMTM6, CD163, and CXCR2, all of which contribute to tumor immune evasion.
Conclusion
Dual blockade of WEE1 and ATM might be a potential therapeutic strategy for PC. Taken toget

Citations

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  • The Killer’s Web: Interconnection between Inflammation, Epigenetics and Nutrition in Cancer
    Marisabel Mecca, Simona Picerno, Salvatore Cortellino
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Effect of Platinum-Based Chemotherapy on PD-L1 Expression on Tumor Cells in Non-small Cell Lung Cancer
Junghoon Shin, Jin-Haeng Chung, Se Hyun Kim, Kyu Sang Lee, Koung Jin Suh, Ji Yun Lee, Ji-Won Kim, Jeong-Ok Lee, Jin-Won Kim, Yu-Jung Kim, Keun-Wook Lee, Jee Hyun Kim, Soo-Mee Bang, Jong-Seok Lee
Cancer Res Treat. 2019;51(3):1086-1097.   Published online November 5, 2018
DOI: https://doi.org/10.4143/crt.2018.537
AbstractAbstract PDFPubReaderePub
Purpose
Programmed death-1 (PD-1)/PD-1 ligand (PD-L1) axis blockades have revolutionized the treatment of advanced non-small cell lung cancer (NSCLC). We assessed the effect of platinum-based chemotherapy on tumor PD-L1 expression and its clinical implications.
Materials and Methods
We used immunohistochemistry to retrospectively evaluate the percentage of tumor cells with membranous PD-L1 staining (tumor proportion score) in paired tumor specimens obtained before and after platinum-based neoadjuvant chemotherapy (NACT) in 86 patients with NSCLC. We analyzed the correlation between the change in PD-L1 tumor proportion score and clinicopathologic characteristics, response to NACT, and survival.
Results
The PD-L1 tumor proportion score increased in a significant proportion of patients with NSCLC after platinum-based NACT (Wilcoxon signed-rank test, p=0.002). That pattern was consistent across clinically defined subgroups except for patients with partial response to NACT. Tumors from 26 patients (30.2%) were PD-L1‒negative before NACT but PD-L1-positive after NACT, whereas the reverse pattern occurred in six patients (7%) (McNemar’s test, p < 0.001). Increase in PD-L1 tumor proportion score was significantly associated with lack of response to NACT (Fisher exact test, p=0.015). There was a tendency, albeit not statistically significant, for patients with an increase in PD-L1 tumor proportion score to have shorter survival.
Conclusion
Tumor PD-L1 expression increased after platinum-based NACT in a significant proportion of patients with NSCLC. Increase in tumor PD-L1 expression may predict poor clinical outcome.

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Immunohistochemistry Biomarkers Predict Survival in Stage II/III Gastric Cancer Patients: From a Prospective Clinical Trial
Min Hwan Kim, Xianglan Zhang, Minkyu Jung, Inkyung Jung, Hyung Soon Park, Seung-Hoon Beom, Hyo Song Kim, Sun Young Rha, Hyunki Kim, Yoon Young Choi, Taeil Son, Hyoung-Il Kim, Jae-Ho Cheong, Woo Jin Hyung, Sung Hoon Noh, Hyun Cheol Chung
Cancer Res Treat. 2019;51(2):819-831.   Published online September 27, 2018
DOI: https://doi.org/10.4143/crt.2018.331
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Identification of biomarkers to predict recurrence risk is essential to improve adjuvant treatment strategies in stage II/III gastric cancer patients. This study evaluated biomarkers for predicting survival after surgical resection.
Materials and Methods
This post-hoc analysis evaluated patients from the CLASSIC trial who underwent D2 gastrectomy with or without adjuvant chemotherapy (capecitabine plus oxaliplatin) at the Yonsei Cancer Center. Tumor expressions of thymidylate synthase (TS), excision repair cross-complementation group 1 (ERCC1), and programmed death-ligand 1 (PD-L1) were evaluated by immunohistochemical (IHC) staining to determine their predictive values.
Results
Among 139 patients, IHC analysis revealed high tumor expression of TS (n=22, 15.8%), ERCC1 (n=23, 16.5%), and PD-L1 (n=42, 30.2%) in the subset of patients. Among all patients, high TS expression tended to predict poor disease-free survival (DFS; hazard ratio [HR], 1.80; p=0.053), whereas PD-L1 positivity was associated with favorable DFS (HR, 0.33; p=0.001) and overall survival (OS; HR, 0.38; p=0.009) in multivariate Cox analysis. In the subgroup analysis, poor DFS was independently predicted by high TS expression (HR, 2.51; p=0.022) in the adjuvant chemotherapy subgroup (n=66). High PD-L1 expression was associated with favorable DFS (HR, 0.25; p=0.011) and OS (HR, 0.22; p=0.015) only in the surgery-alone subgroup (n=73). The prognostic impact of high ERCC1 expression was not significant in the multivariate Cox analysis.
Conclusion
This study shows that high TS expression is a predictive factor for worse outcomes on capecitabine plus oxaliplatin adjuvant chemotherapy, whereas PD-L1 expression is a favorable prognostic factor in locally advanced gastric cancer patients.

Citations

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    Hirofumi Tazawa, Takahisa Suzuki, Akihisa Saito, Akira Ishikawa, Toshiaki Komo, Haruki Sada, Norimitsu Shimada, Naoto Hadano, Takashi Onoe, Takeshi Sudo, Yosuke Shimizu, Kazuya Kuraoka, Hirotaka Tashiro
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Prognostic Role and Clinical Association of Tumor-Infiltrating Lymphocyte, Programmed Death Ligand-1 Expression with Neutrophil-Lymphocyte Ratio in Locally Advanced Triple-Negative Breast Cancer
Jieun Lee, Dong-Min Kim, Ahwon Lee
Cancer Res Treat. 2019;51(2):649-663.   Published online July 31, 2018
DOI: https://doi.org/10.4143/crt.2018.270
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Tumor-infiltrating lymphocyte (TIL), programmed death-ligand 1 (PD-L1) expression and neutrophil-to-lymphocyte ratio (NLR) is associated to immunogenicity and prognosis of breast cancer. We analyzed baseline NLR, changes of NLR, TIL, and PD-L1 during neoadjuvant chemotherapy (NAC) and their clinical implication in triple-negative breast cancer (TNBC).
Materials and Methods
Between January 2008 to December 2015, 358 TNBC patients were analyzed. Baseline NLR, 50 paired NLR (initial diagnosis, after completion of NAC) and 34 paired tissues (initial diagnosis, surgical specimen after completion of NAC) were collected. Changes of TIL, CD4, CD8, forkhead box P3 (FOXP3), and PD-L1 expression were assessed with immunohistochemical stain.
Results
Low NLR (≤ 3.16) was associated to superior survival (overall survival: 41.83 months vs. 36.5 months, p=0.002; disease-free survival [DFS]: 37.85 months vs. 32.14 months, p=0.032). Modest NLR change after NAC (–30% < NLR change < 100%) showed prolonged DFS (38.37 months vs. 22.37 months, p=0.015). During NAC, negative or negative conversion of tumor PD-L1 expression was associated to poor DFS (34.77 months vs. 16.03 months, p=0.037), and same or increased TIL showed trends for superior DFS, but without statistical significance. Positive tumor PD-L1 expression (H-score ≥ 5) in baseline or post- NAC tissue was associated to superior DFS (57.6 months vs. 12.5 months, p=0.001 and 53.3 months vs. 18.9 months, p=0.040). Positive stromal PD-L1 expression in baseline was also associated to superior DFS (50.2 months vs. 20.4 months, p=0.002).
Conclusion
In locally advanced TNBC, baseline NLR, changes of NLR during NAC was associated to survival. Baseline PD-L1 expression and changes of PD-L1 expression in tumor tissue during NAC also showed association to prognosis.

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