Published 6 issues per year
ISSN Print: 1040-8401
ISSN Online: 2162-6472
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CD4+ T Cells in Adoptive Immunotherapy and the Indirect Mechanism of Tumor Rejection
ABSTRACT
Tumor-specific CD4+ effector T cells often play a decisive role in immunologic tumor rejection, in some cases without evident co-participation of CD8+ T cells. During such CD4+ T-cell-mediated rejection there is often no delectable direct contact between T cells and tumor cells. Optimally prepared, adoptively transferred CD4+ T cells can reject established tumors with great efficiency even when targeted tumor cells express no MHC Class II molecules, implying that recognition of tumor antigen (Ag) occurs via MHC Class II-expressing host antigen-presenting cells (APC) within the tumor. Because consequent rejection also excludes Ag-specific contact between CD4+ T cells and MHC Class IIneg tumor cells, the most critical CD4+ T-cell-mediated event is likely cytokine release, resulting in an accumulation and activation of accessory cells such as tumoricidal macrophages and lymphokine-activated killer cells. Although such an indirect rejection mechanism may appear antithetical to popular strategies centered on CD8+ cytotoxic T cells (CTL), current evidence suggests that even CD8+ T-cell-mediated recognition/rejection often bypasses direct tumor cell contact and is largely cytokine mediated. While CTL are likely to participate prominently in many models of tumor rejection, indirect mechanisms of recognition/ rejection have the theoretical advantage of remaining operative even when individual tumor cells evade direct contact by down-regulating MHC and/or Ag expression
-
Visioni Anthony, Zhang Mei, Graor Hallie, Kim Julian, Expansion of melanoma-specific T cells from lymph nodes of patients in stage III: Implications for adoptive immunotherapy in treating cancer, Surgery, 152, 4, 2012. Crossref
-
Ehlken Hanno, Schadendorf Dirk, Eichmüller Stefan, Humoral immune response against melanoma antigens induced by vaccination with cytokine gene-modified autologous tumor cells, International Journal of Cancer, 108, 2, 2004. Crossref
-
Takamura Yukio, Ikeda Hideyuki, Kanaseki Takayuki, Toyota Minoru, Tokino Takashi, Imai Kohzoh, Houkin Kiyohiro, Sato Noriyuki, Regulation of MHC class II expression in glioma cells by class II transactivator (CIITA), Glia, 45, 4, 2004. Crossref
-
Homma Sadamu, Komita Hideo, Sagawa Yukiko, Ohno Tsuneya, Toda Gotaro, Antitumour activity mediated by CD4+ cytotoxic T lymphocytes against MHC class II-negative mouse hepatocellular carcinoma induced by dendritic cell vaccine and interleukin-12, Immunology, 115, 4, 2005. Crossref
-
Knutson K. L., Disis M. L., Tumor antigen-specific T helper cells in cancer immunity and immunotherapy, Cancer Immunology, Immunotherapy, 54, 8, 2005. Crossref
-
Zhao Yong, Sun Yimin, Niu Zeqing, Li Qinghuan, Peng Jianxiao, Wang Junjie, Langnas Alan N., A Novel Approach to Generate Host Antitumor T Cells: Adoptive Immunotherapy by T cells Maturing in Xenogeneic thymus, Journal of Immunotherapy, 30, 1, 2007. Crossref
-
Zhao Yangbing, Zheng Zhili, Khong Hung T., Rosenberg Steven A., Morgan Richard A., Transduction of an HLA-DP4–restricted NY-ESO-1–specific TCR into Primary Human CD4+ Lymphocytes, Journal of Immunotherapy, 29, 4, 2006. Crossref
-
Shiku Hiroshi, Importance of CD4+ Helper T-cells in Antitumor Immunity, International Journal of Hematology, 77, 5, 2003. Crossref
-
Disis Mary L, Bernhard Helga, Jaffee Elizabeth M, Use of tumour-responsive T cells as cancer treatment, The Lancet, 373, 9664, 2009. Crossref
-
Mitchell Duane A., Fecci Peter E., Sampson John H., Immunotherapy of malignant brain tumors, Immunological Reviews, 222, 1, 2008. Crossref
-
Kennedy Richard, Celis Esteban, Multiple roles for CD4+T cells in anti-tumor immune responses, Immunological Reviews, 222, 1, 2008. Crossref
-
Disis Mary L., Park Kyong Hwa, Immunomodulation of Breast Cancer via Tumor Antigen Specific Th1, Cancer Research and Treatment, 41, 3, 2009. Crossref
-
Rajnavölgyi Éva, Lányi Árpád, , 87, 2003. Crossref
-
Lee Kihyun, Min Hyun Jung, Jang Eun Jung, Hong Jeong-Ho, Hwang Eun Sook, In vivo tumor suppression activity by T cell-specific T-bet restoration, International Journal of Cancer, 127, 9, 2010. Crossref
-
Sugiura Daisuke, Denda-Nagai Kaori, Takeda Kazuyoshi, Irimura Tatsuro, Organ microenvironment plays significant roles through Fas ligand in vaccine-induced CD4+ T cell dependent suppression of tumor growth at the orthotopic site, Cancer Science, 101, 9, 2010. Crossref
-
Marshall Deana, Mitchell Duane A., Graner Michael W., Bigner Darell D., Immunotherapy of brain tumors, in Neuro-Oncology. Vol 104 HCN Series, 104, 2012. Crossref
-
Sznurkowski Jacek Jan, Żawrocki Anton, Emerich Janusz, Biernat Wojciech, Prognostic Significance of CD4+and CD8+T Cell Infiltration Within Cancer Cell Nests in Vulvar Squamous Cell Carcinoma, International Journal of Gynecologic Cancer, 21, 4, 2011. Crossref
-
Shimizu Keiji, Kuriyama Hideyuki, Kjaergaard Jorgen, Lee Walter, Tanaka Hiroshi, Shu Suyu, Comparative Analysis of Antigen Loading Strategies of Dendritic Cells for Tumor Immunotherapy, Journal of Immunotherapy, 27, 4, 2004. Crossref
-
Wojtowicz Malgorzata E., Dunn Barbara K., Umar Asad, Immunologic approaches to cancer prevention—current status, challenges, and future perspectives, Seminars in Oncology, 43, 1, 2016. Crossref
-
Wang Rong-Fu, The role of MHC class II-restricted tumor antigens and CD4+ T cells in antitumor immunity, Trends in Immunology, 22, 5, 2001. Crossref
-
Sundberg Eric J., Sawicki Mark W., Southwood Scott, Andersen Peter S., Sette Alessandro, Mariuzza Roy A., Minor Structural Changes in a Mutated Human Melanoma Antigen Correspond to Dramatically Enhanced Stimulation of a CD4+ Tumor-infiltrating Lymphocyte Line, Journal of Molecular Biology, 319, 2, 2002. Crossref
-
Lv Jizhou, Tao Ning, Wu Hao, Liu Xiaoman, Xu Xia, Xu Yingxin, Qin Zhihai, Selective expansion and enhanced anti-tumor effect of antigen-specific CD4+ T cells by retrovirus-mediated IL-15 expression, Protein & Cell, 2, 7, 2011. Crossref
-
Mahnke Yolanda D, Schirrmacher Volker, A novel tumour model system for the study of long-term protective immunity and immune T cell memory, Cellular Immunology, 221, 2, 2003. Crossref
-
Zhang Wenjing, Tian Xinli, Mumtahana Fidia, Jiao Jun, Zhang Teng, Croce Kimiko Della, Ma Daoxin, Kong Beihua, Cui Baoxia, The existence of Th22, pure Th17 and Th1 cells in CIN and Cervical Cancer along with their frequency variation in different stages of cervical cancer, BMC Cancer, 15, 1, 2015. Crossref
-
Tamai Hidemasa, Watanabe Satoshi, Zheng Rongxiu, Deguchi Katsuya, Cohen Peter A., Koski Gary K., Shu Suyu, Effective treatment of spontaneous metastases derived from a poorly immunogenic murine mammary carcinoma by combined dendritic–tumor hybrid vaccination and adoptive transfer of sensitized T cells, Clinical Immunology, 127, 1, 2008. Crossref
-
Kaufman Howard L, Di Vito Joseph, Hörig Heidi, Immunotherapy for pancreatic cancer: current concepts, Hematology/Oncology Clinics of North America, 16, 1, 2002. Crossref
-
Hayashi Takashi, Tanaka Hiroshi, Tanaka Junta, Wang Rongfu, Averbook Bruce J., Cohen Peter A., Shu Suyu, Immunogenicity and Therapeutic Efficacy of Dendritic–Tumor Hybrid Cells Generated by Electrofusion, Clinical Immunology, 104, 1, 2002. Crossref
-
Tanaka Hiroshi, Shimizu Keiji, Hayashi Takashi, Shu Suyu, Therapeutic immune response induced by electrofusion of dendritic and tumor cells, Cellular Immunology, 220, 1, 2002. Crossref
-
Fang Jinbo, Wang Guiyun, Yang Qiong, Song Jinna, Wang Ye, Wang Li, The potential of phage display virions expressing malignant tumor specific antigen MAGE-A1 epitope in murine model, Vaccine, 23, 40, 2005. Crossref
-
Soto Carolina M., Stone Jennifer D., Chervin Adam S., Engels Boris, Schreiber Hans, Roy Edward J., Kranz David M., MHC-class I-restricted CD4 T cells: a nanomolar affinity TCR has improved anti-tumor efficacy in vivo compared to the micromolar wild-type TCR, Cancer Immunology, Immunotherapy, 62, 2, 2013. Crossref
-
Kiniwa Yukiko, Li Jiang, Wang Mingjun, Sun Chuang, Lee Jeffrey E., Wang Rong-Fu, Wang Helen Y., Bai Xue-feng, Identification of DRG-1 As a Melanoma-Associated Antigen Recognized by CD4+ Th1 Cells, PLOS ONE, 10, 5, 2015. Crossref
-
Wang Rong-Fu, Melanoma antigens recognized by CD4+ T cells, in Tumor Antigens Recognized by T Cells and Antibodies, 2003. Crossref
-
Visioni Anthony, Skitzki Joseph, Technical Considerations for the Generation of Adoptively Transferred T Cells in Cancer Immunotherapy, Cancers, 8, 9, 2016. Crossref
-
Nocera Nadia F., Lee M. Catherine, De La Cruz Lucy M., Rosemblit Cinthia, Czerniecki Brian J., Restoring Lost Anti-HER-2 Th1 Immunity in Breast Cancer: A Crucial Role for Th1 Cytokines in Therapy and Prevention, Frontiers in Pharmacology, 7, 2016. Crossref
-
Li Xiao-Lin, Liu Yong-Yu, Knight David, Odaka Yoshinobu, Mathis J. Michael, Shi Runhua, Glass Jonathan, Zhang Qian-Jin, Unutmaz Derya, Effect of B7.1 Costimulation on T-Cell Based Immunity against TAP-Negative Cancer Can Be Facilitated by TAP1 Expression, PLoS ONE, 4, 7, 2009. Crossref
-
Dasgupta Santanu, Bhattacharya-Chatterjee Malaya, O'Malley Bert W., Chatterjee Sunil K., Recombinant Vaccinia Virus Expressing Interleukin-2 Invokes Anti-tumor Cellular Immunity in an Orthotopic Murine Model of Head and Neck Squamous Cell Carcinoma, Molecular Therapy, 13, 1, 2006. Crossref
-
McNeel Douglas G., Nguyen Lan D., Ellis William J., Higano Celestia S., Lange Paul H., Disis Mary L., Naturally occurring prostate cancer antigen-specific T cell responses of a Th1 Phenotype can be detected in patients with prostate cancer, The Prostate, 47, 3, 2001. Crossref
-
Bowers Jacob S., Nelson Michelle H., Majchrzak Kinga, Bailey Stefanie R., Rohrer Baerbel, Kaiser Andrew D.M., Atkinson Carl, Gattinoni Luca, Paulos Chrystal M., Th17 cells are refractory to senescence and retain robust antitumor activity after long-term ex vivo expansion, JCI Insight, 2, 5, 2017. Crossref
-
Wang Bei, Zaidi Neeha, He Li-Zhen, Zhang Li, Kuroiwa Janelle MY, Keler Tibor, Steinman Ralph M, Targeting of the non-mutated tumor antigen HER2/neu to mature dendritic cells induces an integrated immune response that protects against breast cancer in mice, Breast Cancer Research, 14, 2, 2012. Crossref
-
Su Zhen, Peluso Mario V., Raffegerst Silke H., Schendel Dolores J., Roskrow Marie A., Antigen Presenting Cells Transfected with LMP2a RNA Induce CD4 + LMP2a-specific Cytotoxic T Lymphocytes which Kill via a Fas-independent Mechanism, Leukemia & Lymphoma, 43, 8, 2002. Crossref
-
Gholizadeh Zahra, Tavakkol-Afshari Jalil, Nikpoor Amin Reza, Jalali Seyed Amir, Jaafari Mahmoud Reza, Enhanced immune response induced by P5 HER2/neu-derived peptide-pulsed dendritic cells as a preventive cancer vaccine, Journal of Cellular and Molecular Medicine, 22, 1, 2018. Crossref
-
Rojas Jos� Manuel, McArdle Stephanie E. B., Horton Roger B. V., Bell Matthew, Mian Shahid, Li Geng, Ali Selman A., Rees Robert C., Peptide immunisation of HLA-DR?transgenic mice permits the identification of a novel HLA-DR?1*0101? and HLA-DR?1*0401?restricted epitope from p53, Cancer Immunology, Immunotherapy, 54, 3, 2005. Crossref
-
EVANS DEAN E., WEINBERG ANDREW D., BOOSTING T CELL COSTIMULATION IN CANCER: THE POSSIBILITIES SEEM ENDLESS, International Reviews of Immunology, 22, 2, 2003. Crossref
-
Perez-Diez Ainhoa, Joncker Nathalie T., Choi Kyungho, Chan William F. N., Anderson Colin C., Lantz Olivier, Matzinger Polly, CD4 cells can be more efficient at tumor rejection than CD8 cells, Blood, 109, 12, 2007. Crossref
-
Cohen Peter A., Shu Suyu, Finke James H., Principles of Antitumor Immunity and Tumor-Mediated Immunosuppression, in Melanoma, 2002. Crossref
-
Lee Walter T., Dendritic Cell-Tumor Cell Fusion Vaccines, in Cell Fusion in Health and Disease, 713, 2011. Crossref
-
Hutson Thomas E., Thakkar Snehal, Cohen Peter, Borden Ernest C., Interferons and Interleukin-2: Molecular Basis of Activity and Therapeutic Results, in Renal Cell Carcinoma, 2009. Crossref
-
Muranski Pawel, Boni Andrea, Antony Paul A., Cassard Lydie, Irvine Kari R., Kaiser Andrew, Paulos Chrystal M., Palmer Douglas C., Touloukian Christopher E., Ptak Krzysztof, Gattinoni Luca, Wrzesinski Claudia, Hinrichs Christian S., Kerstann Keith W., Feigenbaum Lionel, Chan Chi-Chao, Restifo Nicholas P., Tumor-specific Th17-polarized cells eradicate large established melanoma, Blood, 112, 2, 2008. Crossref
-
Kayashima Hiroto, Toshima Takeo, Okano Shinji, Taketomi Akinobu, Harada Noboru, Yamashita Yo-ichi, Tomita Yukihiro, Shirabe Ken, Maehara Yoshihiko, Intratumoral Neoadjuvant Immunotherapy Using IL-12 and Dendritic Cells Is an Effective Strategy To Control Recurrence of Murine Hepatocellular Carcinoma in Immunosuppressed Mice, The Journal of Immunology, 185, 1, 2010. Crossref
-
Graziano Daniel F., Finn Olivera J., Tumor Antigens and Tumor Antigen Discovery, in Tumor Immunology and Cancer Vaccines, 123, 2005. Crossref
-
Jensen Shawn M., Fox Bernard A., Tumor Immunology and Cancer Vaccines, in Tumor Immunology and Cancer Vaccines, 123, 2005. Crossref
-
Cohen Peter A., Plautz Gregory E., Finke James H., Shu Suyu, Optimizing T-Cell Adoptive Immunotherapy to Overcome Tumor Evasion, in Cancer Immunotherapy at the Crossroads, 2004. Crossref
-
Plautz Gregory E., Cohen Peter A., Weng David E., Shu Suyu, T-Cell Adoptive Immunotherapy, in Handbook of Cancer Vaccines, 2004. Crossref
-
Cohen Peter A., Koski Gary K., Czerniecki Brian J., Bunting Kevin D., Fu Xin-Yuan, Wang Zhengqi, Zhang Wen-Jun, Carter Charles S., Awad Mohamed, Distel Christopher A., Nagem Hassan, Paustian Christopher C., Johnson Terrence D., Tisdale John F., Shu Suyu, STAT3- and STAT5-dependent pathways competitively regulate the pan-differentiation of CD34pos cells into tumor-competent dendritic cells, Blood, 112, 5, 2008. Crossref
-
Wang Li-Xin, Shu Suyu, Disis Mary L., Plautz Gregory E., Adoptive transfer of tumor-primed, in vitro–activated, CD4+ T effector cells (TEs) combined with CD8+ TEs provides intratumoral TE proliferation and synergistic antitumor response, Blood, 109, 11, 2007. Crossref
-
Faries Mark B., Bedrosian Isabelle, Xu Shuwen, Koski Gary, Roros James G., Moise Mirielle A., Nguyen Hung Q., Engels Friederike H. C., Cohen Peter A., Czerniecki Brian J., Calcium signaling inhibits interleukin-12 production and activates CD83+ dendritic cells that induce Th2 cell development, Blood, 98, 8, 2001. Crossref
-
Gulubova M., Ananiev J., Ignatova M., Halacheva K., Pro-Tumor and Anti-Tumor Functions of IL-17 and of TH17 Cells in Tumor Microenvironment, Acta Medica Bulgarica, 43, 2, 2016. Crossref
-
Stanton Sasha E, Disis Mary L, Designing vaccines to prevent breast cancer recurrence or invasive disease, Immunotherapy, 7, 2, 2015. Crossref
-
KNUTSON K L, DISIS M L, IL-12 enhances the generation of tumour antigen-specific Th1 CD4 T cells during ex vivo expansion, Clinical and Experimental Immunology, 135, 2, 2004. Crossref
-
Kalli Kimberly R., Krco Christopher J., Hartmann Lynn C., Goodman Karin, Maurer Matthew J., Yu Chao, Johnson Elliot M., Erskine Courtney L., Disis Mary L., Wettstein Peter J., Fikes John D., Beebe Melanie, Ishioka Glenn, Knutson Keith L., An HLA-DR–Degenerate Epitope Pool Detects Insulin-like Growth Factor Binding Protein 2–Specific Immunity in Patients with Cancer, Cancer Research, 68, 12, 2008. Crossref
-
Park Kyong Hwa, Gad Ekram, Goodell Vivian, Dang Yushe, Wild Thayer, Higgins Doreen, Fintak Patty, Childs Jennifer, dela Rosa Corazon, Disis Mary L., Insulin-like Growth Factor–Binding Protein-2 Is a Target for the Immunomodulation of Breast Cancer, Cancer Research, 68, 20, 2008. Crossref
-
D'Amico G, Bonamino M, Dander E, Marin V, Basso G, Balduzzi A, Biagi E, Biondi A, T cells stimulated by CD40L positive leukemic blasts-pulsed dendritic cells meet optimal functional requirements for adoptive T-cell therapy, Leukemia, 20, 11, 2006. Crossref
-
Dissanayake Samudra K., Thompson James A., Bosch Jacobus J., Clements Virginia K., Chen Peter W., Ksander Bruce R., Ostrand-Rosenberg Suzanne, Activation of Tumor-specific CD4+ T Lymphocytes by Major Histocompatibility Complex Class II Tumor Cell Vaccines, Cancer Research, 64, 5, 2004. Crossref
-
Gao Y, Whitaker-Dowling P, Griffin J A, Bergman I, Treatment with targeted vesicular stomatitis virus generates therapeutic multifunctional anti-tumor memory CD4 T cells, Cancer Gene Therapy, 19, 4, 2012. Crossref
-
Ivanov Roman, Hagenbeek Anton, Ebeling Saskia, Towards immunogene therapy of hematological malignancies, Experimental Hematology, 34, 3, 2006. Crossref
-
Sussman Jeffrey J., Parihar Robin, Winstead Karen, Finkelman Fred D., Prolonged Culture of Vaccine-Primed Lymphocytes Results in Decreased Antitumor Killing and Change in Cytokine Secretion, Cancer Research, 64, 24, 2004. Crossref
-
Röhn Till A., Reitz Annette, Paschen Annette, Nguyen Xuan D., Schadendorf Dirk, Vogt Anne B., Kropshofer Harald, A Novel Strategy for the Discovery of MHC Class II–Restricted Tumor Antigens: Identification of a Melanotransferrin Helper T-Cell Epitope, Cancer Research, 65, 21, 2005. Crossref
-
Yoshida Ayako, Maruyama Haruhiko, Kumagai Takashi, Amano Teruaki, Kobayashi Fumie, Wang Jinyan, Kuribayashi Kagemasa, Ohta Nobuo, Enhanced UV♀1 tumor growth in CBF1 mice infected with Schistosoma mansoni due to modulation of Th1-like responses, Parasitology International, 51, 2, 2002. Crossref
-
Prabakaran Indira, Menon Chandrakala, Xu Shuwen, Gómez-Yafal Alicia, Czerniecki Brian J., Fraker Douglas L., Mature CD83+ dendritic cells infected with recombinant gp 100 vaccinia virus stimulate potent antimelanoma T cells, Annals of Surgical Oncology, 9, 4, 2002. Crossref
-
Peng Liaomin, Krauss John C., Plautz Gregory E., Mukai Shigehiko, Shu Suyu, Cohen Peter A., T Cell-Mediated Tumor Rejection Displays Diverse Dependence Upon Perforin and IFN-γ Mechanisms That Cannot Be Predicted From In Vitro T Cell Characteristics, The Journal of Immunology, 165, 12, 2000. Crossref
-
Novellino Luisa, Renkvist Nicolina, Rini Francesca, Mazzocchi Arabella, Rivoltini Licia, Greco Angela, Deho Paola, Squarcina Paola, Robbins Paul F., Parmiani Giorgio, Castelli Chiara, Identification of a Mutated Receptor-Like Protein Tyrosine Phosphatase κ as a Novel, Class II HLA-Restricted Melanoma Antigen, The Journal of Immunology, 170, 12, 2003. Crossref
-
Plautz Gregory E., Mukai Shigehiko, Cohen Peter A., Shu Suyu, Cross-Presentation of Tumor Antigens to Effector T Cells Is Sufficient to Mediate Effective Immunotherapy of Established Intracranial Tumors, The Journal of Immunology, 165, 7, 2000. Crossref
-
Kanaseki Takayuki, Ikeda Hideyuki, Takamura Yukio, Toyota Minoru, Hirohashi Yoshihiko, Tokino Takashi, Himi Tetsuo, Sato Noriyuki, Histone Deacetylation, But Not Hypermethylation, Modifies Class II Transactivator and MHC Class II Gene Expression in Squamous Cell Carcinomas, The Journal of Immunology, 170, 10, 2003. Crossref
-
Peng Liaomin, Kjaergaard Jørgen, Plautz Gregory E., Weng David E., Shu Suyu, Cohen Peter A., Helper-Independent, L-Selectinlow CD8+ T Cells with Broad Anti-Tumor Efficacy Are Naturally Sensitized During Tumor Progression, The Journal of Immunology, 165, 10, 2000. Crossref