Immune responses to malignancies

Immune responses to tumor-associated antigens (TAs) are often detectable in tumor-bearing hosts, but they fail to eliminate malignant cells or prevent the development of metastases. Patients with cancer generate robust immune responses to infectious agents (bacteria and viruses) perceived as a “danger signal” but only ineffective weak responses to TAs, which are considered as “self.” This fundamental difference in responses to self versus nonself is further magnified by the ability of tumors to subvert the host immune system. Tumors induce dysfunction and apoptosis in CD8⁺ antitumor effector cells and promote expansion of regulatory T cells, myeloid-derived suppressor cells, or both, which downregulate antitumor immunity, allowing tumors to escape from the host immune system. The tumor escape is mediated by several distinct molecular mechanisms. Recent insights into these mechanisms encourage expectations that a more effective control of tumor-induced immune dysfunction will be developed in the near future. Novel strategies for immunotherapy of cancer are aimed at the protection and survival of antitumor effector cells and also of central memory T cells in the tumor microenvironment.

Key words: Cancer, immunity, tumor escape, immune suppression, effector T cells

Abbreviations used: Anx, Annexin V, APC, Antigen-presenting cell, APM, Antigen-processing machinery, β2 m, β₂-microglobulin, CTL, Cytolytic T lymphocyte, DC, Dendritic cell, FasL, Fas ligand, FOXP3, Forkhead box protein 3, iNOS, Inducible nitric oxide synthase, MDSC, Myeloid-derived suppressor cell, NK, Natural killer, PD-1, Programmed death 1, PD-L1, Programmed death ligand 1, PGE₂, Prostaglandin E₂, ROS, Reactive oxygen species, STAT3, Signal transducer and activator of transcription 3, TA, Tumor-associated antigen, TAM, Tumor-associated macrophage, TCR, T-cell receptor, TIL, Tumor-infiltrating lymphocyte, Treg, Regulatory T, VEGF, Vascular endothelial growth factor