Cancer and the Immune System: Basic Concepts and Targets for Intervention

Abstract

A number of consensuses regarding cancer immunology have recently emerged from both preclinical immunotherapy models and analysis of cancer patients. First and foremost, the natural state of endogenous tumor reactive T cells is characterized by general hyporesponsiveness or anergy. This is likely due to a number of mechanisms that tumors use to induce tolerance as they develop. While many of the newer generation vaccines can effectively transfer antigen to and activate dendritic cells, T-cell tolerance remains a major barrier that is difficult to overcome by vaccination alone. Preclinical models demonstrate that for poorly immunogenic tumors, once tolerance has been established, therapeutic vaccines alone are ineffective at curing animals with a significant established tumor burden. However, combination strategies of vaccination together with inhibitors of immunologic checkpoints and agonists for co-stimulatory pathways are proving capable of overcoming tolerance and generating significant anti-tumor responses even in cases of established metastatic cancer.

Targeting CXCR4-dependent immunosuppressive Ly6C low monocytes improves antiangiogenic therapy in colorectal cancer

“…3 and 4), the effect on adaptive immune cells seems to be indirectly through monocytes and neutrophils via immunosuppressive cytokines such as IL-10. The immune system plays an important role in any cancer treatment directly or indirectly (33)(34)(35)(36)(37)(38)(39). Recently, cancer immunotherapy using immune checkpoint blockers (ICBs) has revolutionized cancer therapy by curing some patients (40)(41)(42).…”

Current progress in immunotherapy for pancreatic cancer

“…Immune-based therapies aim to recruit and activate the host’s T cells that recognize tumor-specific antigens (Laheru, 2005). Specifically, during the process of tumorigenesis, tumor antigens become fundamentally different from normal cellular antigens and are often referred to as neoantigens (Pardoll, 2015). These neoantigens are recognized by the host’s immune system as foreign and are normally eliminated during the process of immunoediting (Pardoll, 2015).…”

The role of gut microbiota in forming a response to immunotherapy of malignant neoplasms: problem state

“…Во многих работах на мышиных моделях была опре-делена ключевая роль микробиоты кишечника в ответе опухоли на химиотерапию и иммунотерапию check-point-ингибиторами (ингибиторами иммунных «точек контро-ля» или регуляторными молекулами ключевых этапов иммунного ответа) [25,[34][35][36][37][38], что было связано с опухоле специфическими Т-клеточными ответами и нако-плением Т-клеток CD8 + [37,[39][40][41]. Также в некоторых исследованиях было показано, что механизм данного взаимодействия опосредован дендритными клетками, увеличивающими прайминг и накопление CD8+ Т-лимфо-цитов в микроокружении опухоли [37,42].…”