General Principles of Immunotherapy for Solid Tumors

Erkan ÖZCANa , İrfan ÇİÇİNa

aTrakya University Faculty of Medicine, Department of Medical Oncology, Edirne, Türkiye

Effective immune response against cancer is a complex approach. Both adaptive and innate immune systems play a role in this process. CD8+ and CD4+ lymphocytes make an ”immune synapse” and distinguish whether an antigen is specific to the body or not. While the immune system recognizes cells that have lost their normal structure, prevents their growth and destroys them before they multiply and form cancer, tumor cells have the ability to escape the immune system and even neutralize the host immune response. Treatments are developed based on immune system activity by examining the effects of cytokines, immune checkpoint inhibition, co-stimulatory receptors agonism, manipulation of T cells, oncolytic viruses, vaccines, and other cells in the tumor microenvironment on the tumor.

Keywords: Immun system; immunotherapy

Referanslar

  1. Coley WB. The treatment of malignant tumors by repeated inoculations of erysipelas. With a report of ten original cases. 1893. Clin Orthop Relat Res. 1991;(262):3-11. [Crossref]
  2. Uptodate (internet). (27 September 2023). [Link]
  3. Paul S, Lal G. The Molecular Mechanism of Natural Killer Cells Function and Its Importance in Cancer Immunotherapy. Front Immunol. 2017;8:1124. [Crossref]  [PubMed]  [PMC]
  4. Savage PA, Leventhal DS, Malchow S. Shaping the repertoire of tumor-infiltrating effector and regulatory T cells. Immunol Rev. 2014;259(1):245-58. [Crossref]  [PubMed]  [PMC]
  5. Laoui D, Van Overmeire E, De Baetselier P, Van Ginderachter JA, Raes G. Functional Relationship between Tumor-Associated Macrophages and Macrophage Colony-Stimulating Factor as Contributors to Cancer Progression. Front Immunol. 2014;5:489. [Crossref]
  6. Choudhuri K, van der Merwe PA. Molecular mechanisms involved in T cell receptor triggering. Semin Immunol. 2007;19(4):255-61. [Crossref]  [PubMed]
  7. Garcia KC, Adams EJ. How the T cell receptor sees antigen--a structural view. Cell. 2005;122(3):333-6. [Crossref]  [PubMed]
  8. Schwartz RH. A cell culture model for T lymphocyte clonal anergy. Science. 1990;248(4961):1349-56. [Crossref]  [PubMed]
  9. Wherry EJ, Kurachi M. Molecular and cellular insights into T cell exhaustion. Nat Rev Immunol. 2015;15(8):486-99. [Crossref]  [PubMed]  [PMC]
  10. Schreiber RD, Old LJ, Smyth MJ. Cancer immunoediting: integrating immunity's roles in cancer suppression and promotion. Science. 2011;331(6024):1565-70. [Crossref]  [PubMed]
  11. Doorduijn EM, Sluijter M, Querido BJ, Oliveira CC, Achour A, Ossendorp F, et al. TAP-independent self-peptides enhance T cell recognition of immune-escaped tumors. J Clin Invest. 2016;126(2):784-94. [Crossref]  [PubMed]  [PMC]
  12. Nakahara R, Maeda K, Aki S, Osawa T. Metabolic adaptations of cancer in extreme tumor microenvironments. Cancer Sci. 2023;114(4):1200-7. [Crossref]  [PubMed]  [PMC]
  13. Skrombolas D, Frelinger JG. Challenges and developing solutions for increasing the benefits of IL-2 treatment in tumor therapy. Expert Rev Clin Immunol. 2014;10(2):207-17. [Crossref]  [PubMed]  [PMC]
  14. Xiong F, Wang Q, Wu GH, Liu WZ, Wang B, Chen YJ. Direct and indirect effects of IFN-α2b in malignancy treatment: not only an archer but also an arrow. Biomark Res. 2022;10(1):69. [Crossref]  [PubMed]  [PMC]
  15. Francisco LM, Salinas VH, Brown KE, Vanguri VK, Freeman GJ, Kuchroo VK, Sharpe AH. PD-L1 regulates the development, maintenance, and function of induced regulatory T cells. J Exp Med. 2009;206(13):3015-29. [Crossref]  [PubMed]  [PMC]
  16. Noel PJ, Boise LH, Thompson CB. Regulation of T cell activation by CD28 and CTLA4. Adv Exp Med Biol. 1996;406:209-17. [Crossref]  [PubMed]
  17. Huard B, Mastrangeli R, Prigent P, Bruniquel D, Donini S, El-Tayar N, et al. Characterization of the major histocompatibility complex class II binding site on LAG-3 protein. Proc Natl Acad Sci U S A. 1997;94(11):5744-9. [Crossref]  [PubMed]  [PMC]
  18. Valerius T, Rösner T, Leusen JHW. CD47 Blockade and Rituximab in Non-Hodgkin's Lymphoma. N Engl J Med. 2019;380(5):496-7. [Crossref]
  19. ElTanbouly MA, Croteau W, Noelle RJ, Lines JL. VISTA: a novel immunotherapy target for normalizing innate and adaptive immunity. Semin Immunol. 2019;42:101308. [Crossref]  [PubMed]  [PMC]
  20. Herrera-Camacho I, Anaya-Ruiz M, Perez-Santos M, Millán-Pérez Peña L, Bandala C, Landeta G. Cancer immunotherapy using anti-TIM3/PD-1 bispecific antibody: a patent evaluation of EP3356411A1. Expert Opin Ther Pat. 2019;29(8):587-93. [Crossref]  [PubMed]
  21. Segal NH, He AR, Doi T, Levy R, Bhatia S, Pishvaian MJ, et al. Phase I Study of Single-Agent Utomilumab (PF-05082566), a 4-1BB/CD137 Agonist, in Patients with Advanced Cancer. Clin Cancer Res. 2018;24(8):1816-23. [Crossref]  [PubMed]
  22. Lu X. OX40 and OX40L Interaction in Cancer. Curr Med Chem. 2021;28(28):5659-73. [Crossref]  [PubMed]
  23. Schaer DA, Cohen AD, Wolchok JD. Anti-GITR antibodies--potential clinical applications for tumor immunotherapy. Curr Opin Investig Drugs. 2010;11(12):1378-86.
  24. Takahashi N, Matsumoto K, Saito H, Nanki T, Miyasaka N, Kobata T, et al. Impaired CD4 and CD8 effector function and decreased memory T cell populations in ICOS-deficient patients. J Immunol. 2009 May 1;182(9):5515-27. [Crossref]  [PubMed]
  25. Puellmann K, Beham AW, Kaminski WE. Cytokine storm and an anti-CD28 monoclonal antibody. N Engl J Med. 2006;355(24):2592-3; author reply 2593-4. [Crossref]
  26. Maus MV, Levine BL. Chimeric Antigen Receptor T-Cell Therapy for the Community Oncologist. Oncologist. 2016;21(5):608-17. [Crossref]  [PubMed]  [PMC]
  27. Andersen R, Donia M, Ellebaek E, Borch TH, Kongsted P, Iversen TZ, et al. Long-Lasting Complete Responses in Patients with Metastatic Melanoma after Adoptive Cell Therapy with Tumor-Infiltrating Lymphocytes and an Attenuated IL2 Regimen. Clin Cancer Res. 2016;22(15):3734-45. [Crossref]  [PubMed]
  28. Zimmerman Z, Maniar T, Nagorsen D. Unleashing the clinical power of T cells: CD19/CD3 bi-specific T cell engager (BiTE®) antibody construct blinatumomab as a potential therapy. Int Immunol. 2015;27(1):31-7. [Crossref]  [PubMed]
  29. Liddy N, Bossi G, Adams KJ, Lissina A, Mahon TM, Hassan NJ, et al. Monoclonal TCR-redirected tumor cell killing. Nat Med. 2012;18(6):980-7. [Crossref]  [PubMed]
  30. Russell SJ, Barber GN. Oncolytic Viruses as Antigen-Agnostic Cancer Vaccines. Cancer Cell. 2018;33(4):599-605. [Crossref]  [PubMed]  [PMC]
  31. Hsia JY, Chen JT, Chen CY, Hsu CP, Miaw J, Huang YS, et al. Prognostic significance of intratumoral natural killer cells in primary resected esophageal squamous cell carcinoma. Chang Gung Med J. 2005;28(5):335-40.
  32. Petty AJ, Yang Y. Tumor-associated macrophages: implications in cancer immunotherapy. Immunotherapy. 2017;9(3):289-302. [Crossref]  [PubMed]  [PMC]
  33. Munn DH, Sharma MD, Mellor AL. Ligation of B7-1/B7-2 by human CD4+ T cells triggers indoleamine 2,3-dioxygenase activity in dendritic cells. J Immunol. 2004;172(7):4100-10. [Crossref]  [PubMed]
  34. Linette GP, Carreno BM. Neoantigen Vaccines Pass the Immunogenicity Test. Trends Mol Med. 2017;23(10):869-71. [Crossref]  [PubMed]  [PMC]
  35. Kantoff PW, Higano CS, Shore ND, Berger ER, Small EJ, Penson DF, et al.; IMPACT Study Investigators. Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N Engl J Med. 2010;363(5):411-22. [Crossref]  [PubMed]