免疫治疗在肿瘤治疗中的应用综述
A Review of Immunotherapy in the Treatment of Tumors
DOI: 10.12677/IS.2024.61001, PDF,    国家科技经费支持
作者: 刘家俊#, 江幸燕#, 吴丽艳：珠海科技学院药学与食品科学学院，广东 珠海
关键词: 免疫治疗；肿瘤；研究进展；Immunotherapy； Tumor； Research Progress
摘要: 癌症是对生命构成最为严重威胁的疾病之一，现有的癌症治疗方法包括手术切除原发肿瘤、放疗和化疗等，但目前防止肿瘤转移扩散的效果并不理想。随着对耐受性、免疫性和免疫抑制调节抗肿瘤免疫反应的认识的不断提高，以及靶向治疗方法的出现，这些成功案例对患者的治愈率和存活率具有相当重大的意义。目前，对于免疫治疗的研究中，许多国内外学者提出了许多切实有效的治疗方法，包括免疫检查点抑制剂、CAR-T细胞疗法、疫苗治疗以及综合免疫治疗策略。为了在实际中更高效便捷地治疗肿瘤，本文综述了现有研究中免疫治疗的原理以及常用的几种免疫疗法，为临床应用提供一定的指导建议。
Abstract: Cancer is one of the most serious life-threatening diseases. Existing cancer treatments, including surgical removal of the primary tumor, radiotherapy and chemotherapy, are not currently effective in preventing metastatic spread of tumors. With the increasing understanding of tolerance, im-munity and immunosuppression to regulate anti-tumor immune responses, and the emergence of targeted therapies, these successes are of considerable significance to the cure rate and survival rate of patients. Currently, many domestic and foreign scholars have proposed many effective ther-apeutic methods for immunotherapy, including immune checkpoint inhibitors, CAR-T cell therapy, vaccine therapy, and comprehensive immunotherapy strategies. In order to treat tumors more effi-ciently and conveniently in practice, this article reviews the principles of immunotherapy and sev-eral commonly used immunotherapies in the existing research, and provides certain guidance for clinical application.
文章引用：刘家俊, 江幸燕, 吴丽艳. 免疫治疗在肿瘤治疗中的应用综述[J]. 免疫学研究, 2024, 6(1): 11-14. https://doi.org/10.12677/IS.2024.61001

参考文献

[1] Marincola, F.M., Jaffee, E.M., Hicklin, D.J. and Ferrone, S. (2000) Escape of Human Solid Tumors from T-Cell Recog-nition: Molecular Mechanisms and Functional Significance. Advances in Immunology, 74, 181-273. [Google Scholar] [CrossRef] 
[2] Mellman, I., Coukos, G. and Dranoff, G. (2011) Cancer Immunotherapy Comes of Age. Nature, 480, 480-489. [Google Scholar] [CrossRef] [PubMed]
[3] Rosenberg, S.A. (2005) Cancer Immunotherapy Comes of Age. Nature Reviews Clinical Oncology, 2, Article No. 115. [Google Scholar] [CrossRef] [PubMed]
[4] Ren, X., Guo, S., Guan, X., Kang, Y., Liu, J. and Yang, X. (2022) Im-munological Classification of Tumor Types and Advances in Precision Combination Immunotherapy. Frontiers in Im-munology, 13, Article ID: 790113. [Google Scholar] [CrossRef] [PubMed]
[5] Chou, CS. and Friedman, A. (2016) Cancer-Immune Interaction. In: Chou, C.S. and Friedman, A., Eds., Introduction to Mathematical Biology, Springer, Cham, 137-146. [Google Scholar] [CrossRef] 
[6] Kareva, I., Luddy, K.A., O’Farrelly, C., Gatenby, R.A. and Brown, J.S. (2021) Predator-Prey in Tumor-Immune Interactions: A Wrong Model or Just an Incomplete One? Frontiers in Immunology, 12, Article ID: 668221. [Google Scholar] [CrossRef] [PubMed]
[7] Schwartz, D.J., Rebeck, O.N. and Dantas, G. (2019) Complex Interactions between the Microbiome and Cancer Immune Therapy. Critical Reviews in Clinical Laboratory Sciences, 56, 567-585. [Google Scholar] [CrossRef] [PubMed]
[8] Perales-Puchalt, A., Wojtak, K., Duperret, E.K., Yang, X., Slager, A.M., Yan, J., Muthumani, K., Montaner, L.J. and Weiner, D.B. (2019) Engineered DNA Vaccination against Follicle-Stimulating Hormone Receptor Delays Ovarian Cancer Progression in Animal Models. Molecular Therapy, 27, 314-325. [Google Scholar] [CrossRef] [PubMed]
[9] Hoteit, M., Oneissi, Z., Reda, R., et al. (2021) Cancer Immunotherapy: A Comprehensive Appraisal of Its Modes of Application. Oncology Letters, 22, 1-18. [Google Scholar] [CrossRef] [PubMed]
[10] Cornel, A.M., Mimpen, I.L. and Nierkens, S. (2020) MHC Class I Downregulation in Cancer: Underlying Mechanisms and Potential Targets for Cancer Immunotherapy. Cancers, 12, Ar-ticle No. 1760. [Google Scholar] [CrossRef] [PubMed]
[11] Sharma, P., Hu-Lieskovan, S., Wargo, J.A. and Ribas, A. (2017) Primary, Adaptive, and Acquired Resistance to Cancer Immunotherapy. Cell, 168, 707-723. [Google Scholar] [CrossRef] [PubMed]
[12] Schuster, M., Nechansky, A. and Kircheis, R. (2006) Cancer Im-munotherapy. Biotechnology Journal: Healthcare Nutrition Technology, 1, 138-147. [Google Scholar] [CrossRef] [PubMed]
[13] Hanahan, D. (2022) Hallmarks of Cancer: New Dimensions. Cancer Discovery, 12, 31-46. [Google Scholar] [CrossRef] 
[14] Darvin, P., Toor, S.M., Sasidharan Nair, V., et al. (2018) Immune Checkpoint Inhibitors: Recent Progress and Potential Biomarkers. Experimental & Molecular Medicine, 50, 1-11. [Google Scholar] [CrossRef] [PubMed]
[15] 李涛, 张侃, 杨文雨, 等. 免疫检查点抑制剂CTLA-4在实体肿瘤治疗中的临床应用[J]. 协和医学杂志, 2023, 14(3): 652-659.
[16] Hodi, F.S., et al. (2010) Improved Survival with Ipilimumab in Patients with Metastatic Melanoma. The New England Journal of Medicine, 363, 711-723. [Google Scholar] [CrossRef] 
[17] Robert, C., et al. (2011) Ipilimumab plus Dacarbazine for Previously Untreated Metastatic Melanoma. The New England Journal of Medicine, 364, 2517-2526. [Google Scholar] [CrossRef] 
[18] Gibney, G.T., Weiner, L.M. and Atkins, M.B. (2016) Predictive Biomarkers for Checkpoint Inhibitor-Based Immunotherapy. The Lancet Oncology, 17, e542-e551. [Google Scholar] [CrossRef] 
[19] Inokuchi, J. and Eto, M. (2019) Profile of Pembrolizumab in the Treatment of Patients with Unresectable or Metastatic Urothelial Carcinoma. Cancer Management and Research, 11, 4519-4528. [Google Scholar] [CrossRef] 
[20] Sun, X., Roudi, R., Dai, T., et al. (2019) Im-mune-Related Adverse Events Associated with Programmed Cell Death Protein-1 and Programmed Cell Death Ligand 1 Inhibitors for Non-Small Cell Lung Cancer: A Prisma Systematic Review and Meta-Analysis. BMC Cancer, 19, Article No. 558. [Google Scholar] [CrossRef] [PubMed]
[21] Ai, L.L., Chen, J., Yan, H., He, Q.J., Luo, P.H., Xu, Z.F. and Yang, X.C. (2020) Research Status and Outlook of PD-1/PD-L1 Inhibitors for Cancer Therapy. Drug Design, De-velopment and Therapy, 14, 3625-3649. [Google Scholar] [CrossRef] 
[22] Balar, A.V. and Weber, J.S. (2017) PD-1 and PD-L1 Antibodies in Cancer: Current Status and Future Directions. Cancer Immunology, Immunotherapy, 66, 551-564. [Google Scholar] [CrossRef] [PubMed]
[23] 陆林敏, 张卫平. PD-1/PDL-1及CTLA-4抑制剂治疗原发性肝癌的研究进展[J]. 浙江医学, 2018, 40(13): 1516-1519.
[24] Sterner, R.C. and Sterner, R.M. (2021) CAR-T Cell Therapy: Current Limitations and Potential Strategies. Blood Cancer Journal, 11, Article No. 69. [Google Scholar] [CrossRef] [PubMed]
[25] Siddiqi, H.F., Staser, K.W. and Nambudiri, V.E. (2018) Re-search Techniques Made Simple: CAR T-Cell Therapy. Journal of Investigative Dermatology, 138, 2501-2504. [Google Scholar] [CrossRef] [PubMed]
[26] Hill, L.Q., Lulla, P. and Heslop, H.E. (2019) CAR-T Cell Therapy for Non-Hodgkin Lymphomas: A New Treatment Paradigm. Advances in Cell and Gene Therapy, 2, e54. [Google Scholar] [CrossRef] [PubMed]
[27] Langner, E. (2019) CAR T-Cell Therapy for Acute Lymphoblastic Leukemia. The Science Journal of the Lander College of Arts and Sciences, 12, 6.
[28] Hodgson, K., Ferrer, G., Montserrat, E. and Moreno, C. (2011) Chronic Lymphocytic Leukemia and Autoimmunity: A Systematic Review. Haematologica, 96, 752-761. [Google Scholar] [CrossRef] [PubMed]
[29] Todorovic, Z., Todorovic, D., Markovic, V., et al. (2022) CAR T Cell Therapy for Chronic Lymphocytic Leukemia: Successes and Shortcomings. Current Oncology, 29, 3647-3657. [Google Scholar] [CrossRef] [PubMed]
[30] Kumar, S.K., Rajkumar, S.V., Dispenzieri, A., et al. (2008) Improved Survival in Multiple Myeloma and the Impact of Novel Therapies. Blood, 111, 2516-2520. [Google Scholar] [CrossRef] [PubMed]
[31] Ghosh, A., Mailankody, S., Giralt, S.A., et al. (2018) CAR T Cell Therapy for Multiple Myeloma: Where Are We Now and Where Are We Headed? Leukemia and Lymphoma, 59, 2056-2067. [Google Scholar] [CrossRef] [PubMed]
[32] Miliotou, A.N. and Papadopoulou, L.C. (2018) CAR T-Cell Therapy: A New Era in Cancer Immunotherapy. Current Pharmaceutical Biotechnology, 19, 5-18. [Google Scholar] [CrossRef] [PubMed]
[33] Emens, L.A. (2006) Roadmap to a Better Therapeutic Tumor Vaccine. International Reviews of Immunology, 25, 415-443. [Google Scholar] [CrossRef] [PubMed]
[34] Bais, P., Namburi, S., Gatti, D.M., Zhang, X. and Chuang, J.H. (2017) CloudNeo: A Cloud Pipeline for Identifying Patient-Specific Tumor Neoantigens. Bioinformatics, 33, 3110-3112. [Google Scholar] [CrossRef] [PubMed]
[35] Galluzzi, L., Vacchelli, E., Pedro, J.M.B.S., et al. (2014) Classi-fication of Current Anticancer Immunotherapies. Oncotarget, 5, 12472-12508.
[36] Cheever, M.A. and Higano, C.S. (2011) Provenge (Sipuleucel-T) in Prostate Cancer: The First FDA-Approved Therapeutic Cancer Vaccine. Clinical Cancer Research, 17, 3520-3526. [Google Scholar] [CrossRef] 
[37] Butts, C., Socinski, M.A., Mitchell, P.L., et al. (2014) Tecemotide (LBLP25) versus Placebo after Chemoradiotherapy for Stage III Non-Small-Cell Lung Cancer (START): A Randomised, Double-Blind, Phase 3 Trial. The Lancet Oncology, 15, 59-68. [Google Scholar] [CrossRef] 
[38] di Pietro, A., Tosti, G., Ferrucci, P.F. and Testori, A. (2008) Oncophage: Step to the Future for Vaccine Therapy in Melanoma. Expert Opinion on Biological Therapy, 8, 1973-1984. [Google Scholar] [CrossRef] [PubMed]
[39] Xia, W., Wang, J., Xu, Y., Jiang, F. and Xu, L. (2014) L-BLP25 as a Peptide Vaccine Therapy in Non-Small Cell Lung Cancer: A Review. Journal of Thoracic Disease, 6, 1513-1520.
[40] Aurisicchio, L. and Ciliberto, G. (2012) Genetic Cancer Vaccines: Current Status and Perspectives. Expert Opinion on Biological Therapy, 12, 1043-1058. [Google Scholar] [CrossRef] [PubMed]
[41] Conniot, J., Scomparin, A., Peres, C., Yeini, E., Pozzi, S., Matos, A.I., Kleiner, R., Moura, L.I.F., Zupancič, E., Viana, A.S., Doron, H., Gois, P.M.P., Erez, N., Jung, S., Satchi-Fainaro, R. and Florindo, H.F. (2019) Immunization with Mannosylated Nanovaccines and Inhibition of the Im-mune-Suppressing Microenvironment Sensitizes Melanoma to Immune Checkpoint Modulators. Nature Nanotechnology, 14, 891-901. [Google Scholar] [CrossRef] [PubMed]
[42] Zhu, G., Zhang, F., Ni, Q., Niu, G. and Chen, X. (2017) Efficient Nanovaccine Delivery in Cancer Immunotherapy. ACS Nano, 11, 2387-2392. [Google Scholar] [CrossRef] [PubMed]
[43] Goldberg, M.S. (2015) Immunoengineering: How Nanotechnology Can Enhance Cancer Immunotherapy. Cell, 161, 201-204. [Google Scholar] [CrossRef] [PubMed]
[44] Scheetz, L., Park, K.S., Li, Q., Lowenstein, P.R., Castro, M.G., Schwendeman, A. and Moon, J.J. (2019) Engineering Pa-tient-Specific Cancer Immunotherapies. Nature Biomedical Engineering, 3, 768-782. [Google Scholar] [CrossRef] [PubMed]
[45] Wang, H., Sobral, M.C., Zhang, D.K.Y., Cartwright, A.N., Li, A.W., Dellacherie, M.O., Tringides, C.M., Koshy, S.T., Wucherpfennig, K.W. and Mooney, D.J. (2020) Metabolic La-beling and Targeted Modulation of Dendritic Cells. Nature Materials, 19, 1244-1252. [Google Scholar] [CrossRef] [PubMed]
[46] Ukidve, A., Zhao, Z., Fehnel, A., Krishnan, V., Pan, D.C., Gao, Y., Mandal, A., Muzykantov, V. and Mitragotri, S. (2020) Erythrocyte-Driven Immunization via Biomimicry of Their Natural Antigen-Presenting Function. Proceedings of the National Academy of Sciences of the United States of America, 117, 17727-17736. [Google Scholar] [CrossRef] [PubMed]
[47] Wraith, D.C., Smilek, D.E., Mitchell, D.J., Steinman, L. and McDevitt, H.O. (1989) Antigen Recognition in Autoimmune Encephalomyelitis and the Potential for Peptide-Mediated Immunotherapy. Cell, 59, 247-255. [Google Scholar] [CrossRef] [PubMed]
[48] Xia, Y., Wu, J., Wei, W., Du, Y., Wan, T., Ma, X., An, W., Guo, A., Miao, C., Yue, H., Li, S., Cao, X., Su, Z. and Ma, G. (2018) Exploiting the Pliability and Lateral Mobility of Pickering Emulsion for Enhanced Vaccination. Nature Materials, 17, 187-194. [Google Scholar] [CrossRef] [PubMed]
[49] Singh, M., Singh, A. and Talwar, G.P. (1991) Controlled Delivery of Diphtheria Toxoid Using Biodegradable Poly(D, L-lactide) Microcapsules. Pharmaceutical Research, 8, 958-961. [Google Scholar] [CrossRef] 
[50] Cleland, J.L. (1999) Single-Administration Vaccines: Con-trolled-Release Technology to Mimic Repeated Immunizations. Trends in Biotechnology, 17, 25-29. [Google Scholar] [CrossRef] 
[51] Siegrist, C.A. and Aspinall, R. (2009) B-Cell Responses to Vaccination at the Extremes of Age. Nature Reviews Immunology, 9, 185-194. [Google Scholar] [CrossRef] [PubMed]
[52] Lin, C.Y., Lin, S.J., Yang, Y.C., Wang, D.Y., Cheng, H.F. and Yeh, M.K. (2015) Biodegradable Polymeric Microsphere-Based Vaccines and Their Applications in Infectious Diseases. Human Vaccines & Immunotherapeutics, 11, 650-656. [Google Scholar] [CrossRef] [PubMed]
[53] McLean, H.Q., Thompson, M.G., Sundaram, M.E., Meece, J.K., McClure, D.L., Friedrich, T.C. and Belongia, E.A. (2014) Impact of Repeated Vaccination on Vaccine Effectiveness against Influenza A(H3N2) and B during 8 Seasons. Clinical Infec-tious Diseases, 59, 1375-1385. [Google Scholar] [CrossRef] [PubMed]
[54] Meng, Z., Zhang, Y., She, J., et al. (2021) Ultrasound-Mediated Remotely Controlled Nanovaccine Delivery for Tumor Vaccination and Individualized Cancer Im-munotherapy. Nano Letters, 21, 1228-1237. [Google Scholar] [CrossRef] [PubMed]
[55] Platsoucas, C.D., Fincke, J.E., Pappas, J., et al. (2003) Immune Responses to Human Tumors: Development of Tumor Vaccines. Anticancer Research, 23, 1969-1996.
[56] Rosenberg, S.A., Yang, J.C. and Restifo, N.P. (2004) Cancer Immunotherapy: Moving beyond Current Vaccines. Nature Medicine, 10, 909-915. [Google Scholar] [CrossRef] [PubMed]
[57] Behl, D., Porrata, L.F., Markovic, S.N., Letendre, L., Pruthi, R.K., Hook, C.C., Tefferi, A., Elliot, M.A., Kaufmann, S.H., Mesa, R.A., et al. (2006) Absolute Lymphocyte Count Re-covery after Induction Chemotherapy Predicts Superior Survival in Acute Myelogenous Leukemia. Leukemia, 20, 29-34. [Google Scholar] [CrossRef] [PubMed]
[58] Liseth, K., Ersvaer, E., Hervig, T. and Bruserud, O. (2010) Combina-tion of Intensive Chemotherapy and Anticancer Vaccines in the Treatment of Human Malignancies: The Hematological Experience. Journal of Biomedicine and Biotechnology, 2010, Article ID: 692097. [Google Scholar] [CrossRef] [PubMed]
[59] Shurin, G.V., Tourkova, I.L., Kaneno, R. and Shurin, M.R. (2009) Chemotherapeutic Agents in Noncytotoxic Concentrations Increase Antigen Presentation by Dendritic Cells via an IL-12-Dependent Mechanism. The Journal of Immunology, 183, 137-144. [Google Scholar] [CrossRef] [PubMed]
[60] Tanaka, H., Matsushima, H., Nishibu, A., Clausen, B.E. and Ta-kashima, A. (2009) Dual Therapeutic Efficacy of Vinblastine as a Unique Chemotherapeutic Agent Capable of Inducing Dendritic Cell Maturation. Cancer Research, 69, 6987-6994. [Google Scholar] [CrossRef] 
[61] Herber, D.L., Nagaraj, S., Djeu, J.Y. and Gabrilovich, D.I. (2007) Mechanism and Therapeutic Reversal of Immune Suppression in Cancer. Cancer Research, 67, 5067-5069. [Google Scholar] [CrossRef] 
[62] Ramakrishnan, R., Assudani, D., Nagaraj, S., Hunter, T., Cho, H.I., Antonia, S., Altiok, S., Celis, E. and Gabrilovich, D.I. (2010) Chemotherapy Enhances Tumor Cell Suscepti-bility to CTL-Mediated Killing during Cancer Immunotherapy in Mice. The Journal of Clinical Investigation, 120, 1111-1124. [Google Scholar] [CrossRef] 
[63] Ramakrishnan, R. and Gabrilovich, D.I. (2011) Mechanism of Synergistic Effect of Chemotherapy and Immunotherapy of Cancer. Cancer Immunology, Immunotherapy, 60, 419-423. [Google Scholar] [CrossRef] [PubMed]
[64] Bernstein, M.B., Krishnan, S., Hodge, J.W. and Chang, J.Y. (2016) Immunotherapy and Stereotactic Ablative Radiotherapy (ISABR): A Curative Approach? Nature Reviews Clinical Oncology, 13, 516-524. [Google Scholar] [CrossRef] [PubMed]
[65] Demaria, S., Golden, E.B. and Formenti, S.C. (2015) Role of Local Radiation Therapy in Cancer Immunotherapy. JAMA Oncology, 1, 1325-1332. [Google Scholar] [CrossRef] [PubMed]
[66] Gameiro, S.R., Jammeh, M.L., Wattenberg, M.M., Tsang, K.Y., Ferrone, S. and Hodge, J.W. (2014) Radiation Induced Immunogenic Modulation of Tumor Enhances Antigen Pro-cessing and Calreticulin Exposure, Resulting in Enhanced T-Cell Killing. Oncotarget, 5, 403-416. [Google Scholar] [CrossRef] [PubMed]
[67] Galluzzi, L., Buque, A., Kepp, O., Zitvogel, L. and Kroemer, G. (2017) Immunogenic Cell Death in Cancer and Infectious Disease. Nature Reviews Immunology, 17, 97-111. [Google Scholar] [CrossRef] [PubMed]
[68] Blank, C.U., Haanen, J.B., Ribas, A. and Schumacher, T.N. (2016) Can-cer Immunology. The “Cancer Immunogram”. Science, 352, 658-660. [Google Scholar] [CrossRef] [PubMed]
[69] Lugade, A.A., Sorensen, E.W., Gerber, S.A., Moran, J.P., Frelinger, J.G. and Lord, E.M. (2008) Radiation-Induced IFN-Gamma Production within the Tumor Microenvironment Influences Antitumor Immunity. The Journal of Immunology, 180, 3132-3139. [Google Scholar] [CrossRef] [PubMed]
[70] Chakraborty, M., Abrams, S.I., Camphausen, K., Liu, K., Scott, T., Coleman, C.N., et al. (2003) Irradiation of Tumor Cells Up-Regulates Fas and Enhances CTL Lytic Activity and CTL Adoptive Immunotherapy. The Journal of Immunology, 170, 6338-6347. [Google Scholar] [CrossRef] [PubMed]
[71] Garnett, C.T., Palena, C., Chakraborty, M., Tsang, K.Y., Schlom, J. and Hodge, J.W. (2004) Sublethal Irradiation of Human Tumor Cells Modulates Phenotype Resulting in En-hanced Killing by Cytotoxic T Lymphocytes. Cancer Research, 64, 7985-7994. [Google Scholar] [CrossRef] 
[72] Reits, E.A., Hodge, J.W., Herberts, C.A., Groothuis, T.A., Chakraborty, M., Wansley, E.K., et al. (2006) Radiation Modulates the Peptide Repertoire, Enhances MHC Class I Ex-pression, and Induces Successful Antitumor Immunotherapy. Journal of Experimental Medicine, 203, 1259-1271. [Google Scholar] [CrossRef] [PubMed]
[73] Dewan, M.Z., Galloway, A.E., Kawashima, N., Dewyngaert, J.K., Babb, J.S., Formenti, S.C., et al. (2009) Fractionated but Not Single-Dose Radiotherapy Induces an Immune-Mediated Abscopal Effect When Combined with Anti-CTLA-4 Antibody. Clinical Cancer Research, 15, 5379-5388. [Google Scholar] [CrossRef] 
[74] Demaria, S., Kawashima, N., Yang, A.M., Devitt, M.L., Babb, J.S., Allison, J.P., et al. (2005) Immune-Mediated Inhibition of Metastases after Treatment with Local Radiation and CTLA-4 Blockade in a Mouse Model of Breast Cancer. Clinical Cancer Research, 11, 728-734. [Google Scholar] [CrossRef] [PubMed]
[75] Belcaid, Z., Phallen, J.A., Zeng, J., See, A.P., Mathios, D., Gottschalk, C., et al. (2014) Focal Radiation Therapy Combined with 4-1BB Activation and CTLA-4 Blockade Yields Long-Term Survival and a Protective Antigen-Specific Memory Response in a Murine Glioma Model. PLOS ONE, 9, e101764. [Google Scholar] [CrossRef] [PubMed]
[76] Wu, L., Wu, M.O., De la Maza, L., Yun, Z., Yu, J., Zhao, Y., et al. (2015) Targeting the Inhibitory Receptor CTLA-4 on T Cells Increased Abscopal Effects in Murine Mes-othelioma Model. Oncotarget, 6, 12468-12480. [Google Scholar] [CrossRef] [PubMed]
[77] Twyman-Saint Victor, C., Rech, A.J., Maity, A., Rengan, R., Pauken, K.E., Stelekati, E., et al. (2015) Radiation and Dual Checkpoint Blockade Activate Non-Redundant Immune Mechanisms in Cancer. Nature, 520, 373-377. [Google Scholar] [CrossRef] [PubMed]
[78] Yoshimoto, Y., Suzuki, Y., Mimura, K., Ando, K., Oike, T., Sato, H., et al. (2014) Radiotherapy-Induced Anti-Tumor Immunity Contributes to the Therapeutic Efficacy of Irradiation and Can Be Augmented by CTLA-4 Blockade in a Mouse Model. PLOS ONE, 9, e92572. [Google Scholar] [CrossRef] [PubMed]
[79] Herter-Sprie, G.S., Koyama, S., Korideck, H., Hai, J., Deng, J., Li, Y.Y., et al. (2016) Synergy of Radiotherapy and PD-1 Blockade in Kras-Mutant Lung Cancer. JCI Insight, 1, e87415. [Google Scholar] [CrossRef] [PubMed]
[80] Dovedi, S.J., Adlard, A.L., Lipowska-Bhalla, G., McKenna, C., Jones, S., Cheadle, E.J., et al. (2014) Acquired Resistance to Fractionated Radiotherapy Can Be Overcome by Concurrent PDL1 Blockade. Cancer Research, 74, 5458-5468. [Google Scholar] [CrossRef] 
[81] Deng, L., Liang, H., Burnette, B., Beckett, M., Darga, T., Weichselbaum, R.R., et al. (2014) Irradiation and Anti-PD-L1 Treat-ment Synergistically Promote Antitumor Immunity in Mice. The Journal of Clinical Investigation, 124, 687-695. [Google Scholar] [CrossRef] 
[82] Zeng, J., See, A.P., Phallen, J., Jackson, C.M., Belcaid, Z., Ruzevick, J., et al. (2013) Anti-PD-1 Blockade and Stereotactic Radiation Produce Long-Term Survival in Mice with Intracranial Glio-mas. International Journal of Radiation Oncology, Biology, Physics, 86, 343-349. [Google Scholar] [CrossRef] [PubMed]
[83] Sharabi, A.B., Nirschl, C.J., Kochel, C.M., Nirschl, T.R., Franci-ca, B.J., Velarde, E., et al. (2015) Stereotactic Radiation Therapy Augments Antigen-Specific PD-1-Mediated Antitumor Immune Responses via Cross-Presentation of Tumor Antigen. Cancer Immunology Research, 3, 345-355. [Google Scholar] [CrossRef] 
[84] Vanneman, M. and Dranoff, G. (2012) Combining Immu-notherapy and Targeted Therapies in Cancer Treatment. Nature Reviews Cancer, 12, 237-251. [Google Scholar] [CrossRef] [PubMed]
[85] Sharma, P. and Allison, J.P. (2015) Immune Checkpoint Targeting in Cancer Therapy: Toward Combination Strategies with Curative Potential. Cell, 161, 205-214. [Google Scholar] [CrossRef] [PubMed]
[86] Ye, F., Dewanjee, S., Li, Y., et al. (2023) Advancements in Clinical Aspects of Targeted Therapy and Immunotherapy in Breast Cancer. Molecular Cancer, 22, Article No. 105. [Google Scholar] [CrossRef] [PubMed]
[87] Tan, A.C., Bagley, S.J., Wen, P.Y., et al. (2021) Systematic Re-view of Combinations of Targeted or Immunotherapy in Advanced Solid Tumors. Journal for Immunotherapy of Cancer, 9, e002459. [Google Scholar] [CrossRef] [PubMed]
[88] Corrales, L., Scilla, K., Caglevic, C., Miller, K., Oliveira, J. and Rolfo, C. (2018) Immunotherapy in Lung Cancer: A New Age in Cancer Treatment. Advances in Experimental Medicine and Biology, 995, 65-95. [Google Scholar] [CrossRef] [PubMed]
[89] Martin-Liberal, J., de Olza, M.O., Hierro, C., Gros, A., Rodon, J. and Tabernero, J. (2017) The Expanding Role of Immunotherapy. Cancer Treatment Reviews, 54, 74-86. [Google Scholar] [CrossRef] [PubMed]
[90] Ventola, C.L. (2017) Cancer Immunotherapy, Part 3: Challenges and Future Trends. PT, 42, 514-521.