Cancer Research and Treatment

Original Articles

T Cells Modified with CD70 as an Alternative Cellular Vaccine for Antitumor Immunity: Sang-Eun Lee, A-Ri Shin, Hyun-Jung Sohn, Hyun-Il Cho, Tai-Gyu Kim; Cancer Res Treat. 2020;52(3):747-763. Published online February 14, 2020; DOI: https://doi.org/10.4143/crt.2019.721

Purpose
Successful tumor eradication primarily depends on generation and maintenance of a large population of tumor-reactive CD8 T cells. Dendritic cells (DCs) are well-known potent antigen-presenting cells and have applied to clinics as potent antitumor therapeutic agents. However, high cost and difficulty in obtaining sufficient amounts for clinical use are the crucial drawbacks of DC-based vaccines. Here, we aimed to develop T cell–based vaccine capable of eliciting potent antitumor therapeutic effects by providing effective costimulatory signals.
Materials and Methods
Antigenic peptide-loaded T cells transfected with retrovirus encoding costimulatory ligands CD70, CD80, OX40L, or 4-1BBL were assessed for antigen-specific CD8 T-cell responses and evaluated antitumor effects along with immunization of a mixture of synthetic peptides, poly-IC and anti-CD40 antibodies (TriVax).
Results
T cells expressing CD70 (CD70-T) exhibited similar level of stimulatory functionality and therapeutic efficacy as DCs. Moreover, CD70-T prime followed by TriVax booster heterologous vaccination elicited therapeutic antitumor effect against B16 melanoma where mediated by CD8 T cells but not CD4 T cells or natural killer cells. The combination with programmed death-ligand 1 blockade led to potent therapeutic efficacy which exhibited increased tumor-infiltrating CD8 T cells. CD70-T pulsed with multi-antigenic peptide generated multiple antigen-specific polyvalent CD8 T cells that were capable of inhibiting tumor growth effectively. Moreover, CD70-T vaccination resulted in higher expansion and migration of adoptively transferred T cells into tumor sites and elicits enhanced therapeutic effects with peptide-based booster immu-nization.
Conclusion
These results imply that T cells endowed with CD70 enable the design of effective vaccination strategies against solid cancer, which may overcome current limitations of DC-based vaccines.

Citations

Citations to this article as recorded by

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Jian Lu, Feng Ding, Yongjie Sun, Yu Zhao, Wenbiao Ma, Huan Zhang, Bo Shi
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Amplifying mRNA vaccines: potential versatile magicians for oncotherapy
Chaoying Hu, Jianyang Liu, Feiran Cheng, Yu Bai, Qunying Mao, Miao Xu, Zhenglun Liang
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STING activation normalizes the intraperitoneal vascular-immune microenvironment and suppresses peritoneal carcinomatosis of colon cancer
Seung Joon Lee, Hannah Yang, Woo Ram Kim, Yu Seong Lee, Won Suk Lee, So Jung Kong, Hye Jin Lee, Jeong Hun Kim, Jaekyung Cheon, Beodeul Kang, Hong Jae Chon, Chan Kim
Journal for ImmunoTherapy of Cancer.2021; 9(6): e002195. CrossRef
Comprehensive Analysis of the Prognostic Value and Immune Function of Immune Checkpoints in Stomach Adenocarcinoma
Kai Shen, Tong Liu
International Journal of General Medicine.2021; Volume 14: 5807. CrossRef

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Alpha-Type 1 Polarized Dendritic Cells Loaded with Apoptotic Allogeneic Breast Cancer Cells Can Induce Potent Cytotoxic T Lymphocytes against Breast Cancer: Min-Ho Park, Deok-Hwan Yang, Mi-Hyun Kim, Jae-Hong Jang, Yoon-Young Jang, Youn-Kyung Lee, Chun-Ji Jin, Than Nhan Nguyen Pham, Truc Anh Nguyen Thi, Mi-Seon Lim, Hyun-Ju Lee, Cheol Yi Hong, Jung-Han Yoon, Je-Jung Lee; Cancer Res Treat. 2011;43(1):56-66. Published online March 31, 2011; DOI: https://doi.org/10.4143/crt.2011.43.1.56

Abstract PDF PubReader ePub

PURPOSE
Various tumor antigens can be loaded onto dendritic cells (DCs) to induce a potent cytotoxic T lymphocyte (CTL) response in DC-based immunotherapy against breast cancer. However, in the clinical setting, obtaining a sufficient number of autologous tumor cells as a source of tumor antigens is a laborious process. We therefore investigated the feasibility of immunotherapy using breast-cancer-specific CTLs generated in vitro by use of alpha-type 1 polarized DCs (alpha DC1s) loaded with ultraviolet B-irradiated cells of the breast cancer cell line MCF-7.
MATERIALS AND METHODS
alphaDC1s were induced by loading allogeneic tumor antigen generated from the MCF-7 UVB-irradiated breast cancer cell line. Antigen-pulsed alphaDC1s were evaluated by morphological and functional assays, and the breast-cancer-specific CTL response was analyzed by cytotoxic assay.
RESULTS
The alphaDC1s significantly increased the expression of several molecules related to DC maturation without differences according to whether the alphaDC1s were loaded with tumor antigens. The alphaDC1s showed a high production of interleukin-12 both during maturation and after subsequent stimulation with CD40L, which was not significantly affected by loading with tumor antigens. Breast-cancer-specific CTLs against autologous breast cancer cells were successfully induced by alphaDC1s loaded with apoptotic MCF-7 cells.
CONCLUSION
Autologous DCs loaded with an allogeneic breast cancer cell line can generate potent breast-cancer-specific CTL responses. This may be a practical method for cellular immunotherapy in patients with breast cancer.

Citations

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Usefulness of IL-21, IL-7, and IL-15 conditioned media for expansion of antigen-specific CD8+ T cells from healthy donor-PBMCs suitable for immunotherapy
Julián A. Chamucero-Millares, David A. Bernal-Estévez, Carlos A. Parra-López
Cellular Immunology.2021; 360: 104257. CrossRef
Extending traditional antibody therapies: Novel discoveries in immunotherapy and clinical applications
Charles Shin, Sung Soo Kim, Yong Hwa Jo
Molecular Therapy - Oncolytics.2021; 22: 166. CrossRef
Enhanced Human T Lymphocyte Antigen Priming by Cytokine-Matured Dendritic Cells Overexpressing Bcl-2 and IL-12
Hui Zhang, Yu Wang, Qian-Ting Wang, Sheng-Nan Sun, Shi-You Li, Hong Shang, You-Wen He
Frontiers in Cell and Developmental Biology.2020;[Epub] CrossRef
Tumor lysate-loaded Bacterial Ghosts as a tool for optimized production of therapeutic dendritic cell-based cancer vaccines
N. Dobrovolskienė, V. Pašukonienė, A. Darinskas, J.A. Kraśko, K. Žilionytė, A. Mlynska, Ž. Gudlevičienė, E. Mišeikytė-Kaubrienė, V. Schijns, W. Lubitz, P. Kudela, M. Strioga
Vaccine.2018; 36(29): 4171. CrossRef
Antitumor dendritic cell–based vaccines: lessons from 20 years of clinical trials and future perspectives
João Constantino, Célia Gomes, Amílcar Falcão, Maria T. Cruz, Bruno M. Neves
Translational Research.2016; 168: 74. CrossRef
Identification of proteins derived from Listeria monocytogenes inducing human dendritic cell maturation
Reza Mirzaei, Azad Saei, Fatemeh Torkashvand, Bahareh Azarian, Ahmad Jalili, Farshid Noorbakhsh, Behrouz Vaziri, Jamshid Hadjati
Tumor Biology.2016; 37(8): 10893. CrossRef
Dendritic Cell-Based Cancer Immunotherapy against Multiple Myeloma: From Bench to Clinic
My-Dung Hoang, Sung-Hoon Jung, Hyun-Ju Lee, Youn-Kyung Lee, Thanh-Nhan Nguyen-Pham, Nu-Ri Choi, Manh-Cuong Vo, Seung-Shin Lee, Jae-Sook Ahn, Deok-Hwan Yang, Yeo-Kyeoung Kim, Hyeoung-Joon Kim, Je-Jung Lee
Chonnam Medical Journal.2015; 51(1): 1. CrossRef
Dendritic Cells Induce Specific Cytotoxic T Lymphocytes against Prostate Cancer TRAMP-C2 Cells Loaded with Freeze-thaw Antigen and PEP-3 Peptide
Xiao-Qi Liu, Rong Jiang, Si-Qi Li, Jing Wang, Fa-Ping Yi
Asian Pacific Journal of Cancer Prevention.2015; 16(2): 571. CrossRef
Branched Polyethylenimine-Superparamagnetic Iron Oxide Nanoparticles (bPEI-SPIONs) Improve the Immunogenicity of Tumor Antigens and Enhance Th1 Polarization of Dendritic Cells
My-Dung Hoang, Hwa-Jeong Lee, Hyun-Ju Lee, Sung-Hoon Jung, Nu-Ri Choi, Manh-Cuong Vo, Thanh-Nhan Nguyen-Pham, Hyeoung-Joon Kim, In-Kyu Park, Je-Jung Lee
Journal of Immunology Research.2015; 2015: 1. CrossRef
Generation of Potent Cytotoxic T Lymphocytes Against Castration‐Resistant Prostate Cancer Cells by Dendritic Cells Loaded With Dying Allogeneic Prostate Cancer Cells
E. C. Hwang, M.‐S. Lim, C.‐M. Im, D.‐D. Kwon, H.‐J. Lee, T.‐N. Nguyen‐Pham, Y.‐K. Lee, J.‐J. Lee
Scandinavian Journal of Immunology.2013; 77(2): 117. CrossRef
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Arpit Bhargava, Dinesh Mishra, Smita Banerjee, Pradyumna Kumar Mishra
Immunotherapy.2012; 4(7): 703. CrossRef

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Altered Expression of Smad Proteins in T or NK-cell Lymphomas: Jai Hyang Go; Cancer Res Treat. 2008;40(4):197-201. Published online December 31, 2008; DOI: https://doi.org/10.4143/crt.2008.40.4.197

Abstract PDF PubReader ePub

Purpose

Smad proteins mediate cellular signaling through the transforming growth factor-β family (TGF-βs). Smads 2 and 3 transmit signals from TGF-β, and Smad4 is a common mediator, as well. However, little is known concerning the expression patterns of Smads in lymphoid tissue.

Materials and Methods

Immunohistochemistry for Smad3 and Smad4 was performed on paraffin-embedded tissue sections collected from 26 T- or NK-cell lymphomas.

Results

Nearly all cells in germinal centers were positive for Smad3, and more than 50% of paracortical cells were positive for Smad3 in reactive lymphoid tissue. When Smad4 immunostaining was conducted, nearly all the cells in the germinal centers showed diffuse cytoplasmic staining, and most of them exhibited nuclear positivity, as well. In addition, more than 50% of the cells in the paracortex were positive for Smad4. Furthermore, the Smad3 staining pattern was preserved in all malignant lymphomas, but four of these cases (15%) exhibited decreased expression of Smad4. All lymphoblastic lymphomas showed strong positivity in most of tumor cells, but one unspecified peripheral lymphoma, two nasal NK/T cell lymphomas, and one anaplastic large cell lymphoma were negative for Smad4.

Conclusions

These results suggest that TGF-β-specific Smads may be actively involved in signal transduction in lymphoid organs and that Smad-mediated TGF-β signaling pathways are operative in malignant lymphoma. In addition, loss of Smad4 expression might be associated with development of some T-cell lymphomas.

Citations

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Appreciating the broad clinical features of SMAD4 mutation carriers: a multicenter chart review
Karen E. Wain, Marissa S. Ellingson, Jamie McDonald, Amanda Gammon, Maegan Roberts, Pavel Pichurin, Ingrid Winship, Douglas L. Riegert-Johnson, Jeffrey N. Weitzel, Noralane M. Lindor
Genetics in Medicine.2014; 16(8): 588. CrossRef
Genomic profiling combined with gene expression profiling in primary central nervous system lymphoma
Chang Ohk Sung, Sang Cheol Kim, Sivasundaram Karnan, Kennosuke Karube, Hyung Jin Shin, Do-Hyun Nam, Yeon-Lim Suh, Seok-Hyung Kim, Ji Yeon Kim, Seok Jin Kim, Won Seog Kim, Masao Seto, Young-Hyeh Ko
Blood.2011; 117(4): 1291. CrossRef

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Distribution of Langerhans Cells Associated with T Lymphocytes in Primary Lung Cancer: Dong Hwan Shin, Kyung Young Chung, Byung Soo Kim, Kwang Hwa Park; J Korean Cancer Assoc. 1996;28(2):272-281.

Abstract PDF: We have studied the distribution of Langerhans cells associated with T lymphocytes/or histocytes in 83 cases of resected primary lung cancers by immunohistochemical methods using anti-S100 protein, B and T lymphocyte markers and anti-lysozyme antibodies. Langerhans cells were present in all the main histologic subtypes but small cell carcinoma. Langerhans cells were noted much more frequently in adenocarcinoma, particularly those subclassified as bronchioloalveolar carcinoma than in other histologic types. T lymphocytes were seen if any associated with Langerhans cells among tumor cells whereas lysozyme positive histiocytes were mostly scattered in the supporting stroma between tumor cells. Clinical follow-up data available for 72 cases showed no significant correlations between infiltration of Langerhans cells and overall survival. There seemed to be a little longer survival in adenocarcinoma with Langerhans cells than those without but it proved to be insignificant by statistical analysis. The current results remain to be confirmed in much larger studies with regard to prognostic significance of infiltrating Langerhans cells and their association with T lymphocytes in primary lung cancers in view of known immunologic role of Langerhans cells.

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