Role of the tumor immune microenvironment in tumor immunotherapy (Review)

Abstract

Tumor immunotherapy is considered to be a novel and promising therapy for tumors and it has recently become a hot research topic. The clinical success of tumor immunotherapy has been notable, but it has been less than totally satisfactory because tumor immunotherapy has performed poorly in numerous patients although it has shown appreciable efficacy in some patients. A minority of patients demonstrate durable responses but the majority of patients do not respond to tumor immunotherapy as the tumor immune microenvironment is different in different patients for different tumor types. The success of tumor immunotherapy may be affected by the heterogeneity of the tumor immune microenvironment and its components, as these vary widely during neoplastic progression. The deepening of research and the development of technology have improved our understanding of the complexity and heterogeneity of the tumor immune microenvironment and its components, and their effects on response to tumor immunotherapy. Therefore, investigating the tumor immune microenvironment and its components and elucidating their association with tumor immunotherapy should improve the ability to study, predict and guide immunotherapeutic responsiveness, and uncover new therapeutic targets.

Recent Advances and Challenges in Cancer Immunotherapy

“…The TME is heterogenous and varies by patient, cancer subtype and stage. TME composition influences cancer immunotherapy patient responses [ 8 ]. To improve immunotherapy efficacy, it is critical to understand TME cellularity and functionally.…”

“…Tumor cells can generate chronic, weak antigen signals that drive T-cell reprogramming into an unresponsive, transcriptionally “exhausted” state. They also deplete nutrients and accumulate waste products, such as lactate and kynurenine, which inhibit T cells and create a hostile environment for effector cells [ 5 , 8 ] ( Figure 1 , created with , accessed on 15 August 2022).…”

“…TILs include CD8+ CTLs, CD4+ T-helper cells, Tregs, innate lymphoid cells (ILCs), NK cells and natural killer T (NKT) cells. CD8:CD4 TIL ratios have been studied as biomarkers in metastatic melanoma, NSCLC and colon cancer, with certain ratios correlating with increased ICI response predictions, diagnosis and survival rates in patients [ 1 , 8 , 135 , 136 ]. Immunologically “hot” tumors have heavy TIL infiltration.…”

“…T-cell exhaustion is an area that has been extensively researched. Exhausted T cells can be “pre-exhausted” or “terminally exhausted” with increasing expression of immune checkpoints, such as CTLA-4, PD-1, Tim-3, lymphocyte activation gene-3 (LAG-3) and TIGIT, denoting a more terminally exhausted state [ 8 ]. Poor self-renewal, disrupted metabolism and gradual effector function loss characterize these cells [ 5 , 131 ].…”

“…Tumor–host immune system interactions are heterogenous and certain characteristics can predict immunotherapy responsiveness. The tumor microenvironment (TME), in particular, affects immunotherapeutic response and immune evasion [ 8 , 9 ]. A deep understanding of host–tumor interactions is critical to fostering the development of novel and more effective immunotherapies.…”