Cancer immunotherapy: current opportunities and perspectives


  • O.Yu. Nikolaeva Bogomolets National Medical University, Kyiv, Ukraine
  • R.V. Liubota Bogomolets National Medical University, Kyiv, Ukraine
  • O.S. Zotov Bogomolets National Medical University, Kyiv, Ukraine
  • R.I. Vereshchako Bogomolets National Medical University, Kyiv, Ukraine



cancer immunotherapy, cytokines, immune checkpoint inhibitors, adaptive T-cell therapy, review


Cancer immunotherapy is a relatively new and pro­mising method of treating neoplasms. Understanding the antigen-directed cytotoxicity of T-lymphocytes has become one of the central directions in involving the immune system in the fight against cancer. Basic research in this area has led to the invention of checkpoint inhibitors, adoptive T-cell therapy, and cancer vaccines. Cytokines can enhance the action of T-lymphocytes for their ability to directly stimulate effector and stromal cells in tumor focus and enhance recognition of tumor cells by cytotoxic effector cells. They were the first in cancer immunotherapy and remain relevant to this day. Today, immunotherapy is an effective treatment for most malignant tumors, including melanoma, non-small cell lung cancer, liver, stomach, bladder, cervical cancer, some types of breast cancer, lymphoma, etc. However, immunotherapy of some malignant tumors is ineffective, therefore, the development of new and improvement of existing immunotherapy agents is actively underway, and there is a hope that the indications for its use will expand. For this purpose, this review discusses the principles of action of various classes of immunotherapeutic anticancer agents, namely cytokines, immune checkpoint inhibitors, and adaptive T-cell therapy. The work highlights their indications, efficacy and toxicity from the use of each class of drugs, as well as the prospects for the development of immunotherapeutic anticancer drugs.


Sung H., Ferlay J., Siegel R.L., Laversanne M., Soerjomataram I., Jemal A., Bray F. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 2021. 71(3). 209-249.

Ventola C. Lee. Cancer Immunotherapy, Part 1: Current Strategies and Agents. P&T. 2017. 42(6). 375-383.

Lee S., Margolin K. Cytokines in cancer immunotherapy. Cancers (Basel). 2011. 3(4). 3856-93.

Zhao Z., Zheng L., Chen W., Weng W., Song J., Ji J. Delivery strategies of cancer immunotherapy: recent advances and future perspectives. J. Hematol. Oncol. 2019. 12(1). 126.

Parker B.S., Rautela J., Hertzog P.J. Antitumour actions of interferons: implications for cancer therapy. Nat. Rev. Cancer. 2016. 16(3). 131-144.

How J., Hobbs G. Use of Interferon Alfa in the Treatment of Myeloproliferative Neoplasms: Perspectives and Review of the Literature. Cancers. 2020. 12(7). 1954.

Malato A., Rossi E., Palumbo G.A., Guglielmelli P., Pugliese N. Drug-Related Cutaneous Adverse Events in Philadelphia Chromosome-Negative Myeloproliferative Neoplasms: A Literature Review. International Journal of Molecular Sciences. 2020. 21(11). 3900.

Fleischmann J.D., Shingleton W.B., Gallagher C., Ratnoff O.D., Chahine A. Fibrinolysis, thrombocytopenia, and coagulation abnormalities complicating high-dose interleukin-2 immunotherapy. J. Lab. Clin. Med. 1991. 117(1). 76-82.

Mahmoudpour S.H., Jankowski M., Valerio L., Becker C., Espinola-Klein C., Konstantinides S. et al. Safety of low-dose subcutaneous recombinant interleukin-2: systematic review and meta-analysis of randomized controlled trials. Scientific Reports. 2019. 9(1). 7145.

Marin-Acevedo J.A., Dholaria B., Soyano A.E., Knutson K.L., Chumsri S., Lou Y. Next generation of immune checkpoint therapy in cancer: new developments and challenges. Journal of Hematology & Oncology. 2018. 11(1).

Alcover A., Alarcón B., Di Bartolo V. Cell Biology of T Cell Receptor Expression and Regulation. Annual Review of Immunology. 2018. 36(1). 103-125.

Najafi M., Goradel N.H., Farhood B., Salehi E., Solhjoo S., Toolee H. et al. Tumor microenvironment: Interactions and therapy. Journal of Cellular Physiology. 2019. 234. 5700-5721.

Alex D. Waldman, Jill M. Fritz, Michael J. Lenardo. A guide to cancer immunotherapy: from T cell basic science to clinical practice. Nat. Rev. Immunology. 2020. 20. 651-668.

Leach D.R., Krummel M.F., Allison J.P. Enhancement of antitumor immunity by CTLA-4 blockade. Science. 1996. 271. 1734-1736.

Development of PD-1 and PD-L1 inhibitors as a form of cancer immunotherapy: a comprehensive review of registration trials and future considerations. J. Immunother. Cancer. 2018. 6. 8.

Iwai Y. et al. Involvement of PD-L1 on tumor cells in the escape from host immune system and tumor immunotherapy by PD-L1 blockade. Proc. Natl. Acad. Sci. USA. 2002. 99. 12293-12297.

Garon E.B. et al. Pembrolizumab for the treatment of non-small-cell lung cancer. N. Engl. J. Med. 2015. 372. 2018-2028.

Ding L., Chen F. Predicting tumor response to PD-1 blo­ckade. N. Engl. J. Med. 2019. 381. 477-479.

Rosenberg J. E. et al. Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy: a single-arm, multicentre, phase 2 trial. Lancet. 2016. 387. 1909-1920.

Bai R., Lv Z., Xu D., Cui J. Predictive biomarkers for cancer immunotherapy with immune checkpoint inhibitors. Biomarker Research. 2020. 8(1).

Fritz J.M., Lenardo M.J. Development of immune checkpoint therapy for cancer. J. Exp. Med. 2019. 216. 1244-1254.

Nishimura H., Minato N., Nakano T., Honjo T. Immunolo­gical studies on PD-1 deficient mice: implication of PD-1 as a negative regulator for B cell responses. Int. Immunol. 1998. 10. 1563-1572.

Kumar V. et al. Current diagnosis and management of immune related adverse events (irAEs) induced by immune checkpoint inhibitor therapy. Front. Pharmacol. 2017. 8. 49.

Wang P.-F. et al. Immune-related adverse events associated with anti-PD-1/PD-L1 treatment for malignancies: a meta-analysis. Front. Pharmacol. 2017. 8. 730.

Rauch D.A. et al. Rapid progression of adult T-cell leukemia/lymphoma as tumor-infiltrating Tregs after PD-1 blockade. Blood. 2019. 134. 1406-1414.

Champiat S. et al. Hyperprogressive disease: recognizing a novel pattern to improve patient management. Nat. Rev. Clin. Oncol. 2018. 15. 748-762.

Zhang Y. et al. Hijacking antibody-induced CTLA-4 lysosomal degradation for safer and more effective cancer immunotherapy. Cell Res. 2019. 29. 609-627.

Riley R.S., June C.H., Langer R., Mitchell M.J. Delivery technologies for cancer immunotherapy. Nat. Rev. Drug. Discov. 2019. 18. 175-196.

Gide T.N., Quek C., Menzies A.M., Tasker A.T., Shang P., Holst J., et al. Distinct Immune Cell Populations Define Response to Anti-PD-1 Monotherapy and Anti-PD-1/Anti-CTLA-4 Combined Therapy. Cancer Cell. 2019. 35(2). 238-255.

Southam C.M., Brunschwig A., Levin A.G., Dizon Q.S. Effect of leukocytes on transplantability of human cancer. Cancer. 1966. 19. 1743-1753.

Weiden P.L. et al. Antileukemic effect of graft-versus host disease in human recipients of allogeneic-marrow grafts. N. Engl. J. Med. 1979. 300. 1068-1073.

Luca Gattinoni et al. Removal of homeostatic cytokine sinks by lymphodepletion enhances the efficacy of adoptively transferred tumor-specific CD8+ T cells. J. Exp. Med. 2005. 7. 907-912.

Rosenberg S.A. et al. Durable complete responses in heavily pretreated patients with metastatic melanoma using T-cell transfer immunotherapy. Clin. Cancer Res. 2011. 17. 4550-4557.

Garrido F., Aptsiauri N., Doorduijn E.M., Garcia Lora A.M., van Hall T. The urgent need to recover MHC class I in cancers for effective immunotherapy. Curr. Opin. Immunol. 2016. 39. 44-51.

Eyquem J. et al. Targeting a CAR to the TRAC locus with CRISPR/Cas9 enhances tumour rejection. Nature. 2017. 543. 113-117.

Brentjens R.J. et al. CD19-targeted T cells rapidly induce molecular remissions in adults with chemotherapy-refractory acute lymphoblastic leukemia. Sci. Transl Med. 2013. 5. 177ra138.

Park J.H. et al. Long-term follow-up of CD19 CAR therapy in acute lymphoblastic leukemia. N. Engl. J. Med. 2018. 378. 449-459.

Fry T.J. et al. CD22-targeted CAR T cells induce remission in B-ALL that is naive or resistant to CD19-targeted CAR immunotherapy. Nat. Med. 2018. 24. 20-28.

Majzner R.G. et al. CAR T cells targeting B7-H3, a pan-cancer antigen, demonstrate potent preclinical activity against pediatric solid tumors and brain tumors. Clin. Cancer Res. 2019. 25. 2560-2574.

Lynn R.C. et al. c-Jun overexpression in CAR T cells induces exhaustion resistance. Nature. 2019. 576. 293-300.

Giavridis T. et al. CAR T cell-induced cytokine release syndrome is mediated by macrophages and abated by IL-1 blockade. Nat. Med. 2018. 24. 731-738.

Hernandez I., Prasad V., Gellad W.F. Total costs of chimeric antigen receptor T-cell immunotherapy. JAMA Oncol. 2018. 4. 994-996.

Conley M.E. et al. Primary B cell immunodeficiencies: comparisons and contrasts. Annu. Rev. Immunol. 2009. 27. 199-227.

Vormittag P., Gunn R., Ghorashian S., Veraitch F.S. A guide to manufacturing CAR T cell therapies. Curr. Opin. Biotechnol. 2018. 53. 164-181.