The Tumor Microenvironment: A Milieu Hindering and Obstructing Antitumor Immune Responses

Abstract

The success of cancer immunotherapy relies on the knowledge of the tumor microenvironment and the immune evasion mechanisms in which the tumor, stroma, and infiltrating immune cells function in a complex network. The potential barriers that profoundly challenge the overall clinical outcome of promising therapies need to be fully identified and counteracted. Although cancer immunotherapy has increasingly been applied, we are far from understanding how to utilize different strategies in the best way and how to combine therapeutic options to optimize clinical benefit. This review intends to give a contemporary and detailed overview of the different roles of immune cells, exosomes, and molecules acting in the tumor microenvironment and how they relate to immune activation and escape. Further, current and novel immunotherapeutic options will be discussed.

Prognostic Role and Clinical Significance of Tumor-Infiltrating Lymphocyte (TIL) and Programmed Death Ligand 1 (PD-L1) Expression in Triple-Negative Breast Cancer (TNBC): A Systematic Review and Meta-Analysis Study

“…However, tumor cells can induce an immunosuppressive tumor microenvironment and evade the anti-tumoral immune responses. The aim of immunotherapy is restoring the anti-tumoral immune responses to reject tumoral cells [6,7]. Immune checkpoints have been implicated in the induction of immunosuppressive tumor microenvironments [7].…”

Immune Escape Mechanisms and Their Clinical Relevance in Head and Neck Squamous Cell Carcinoma

“…The composition and frequency of immune cells within the TME and peripheral blood plays an important role in tumorigenesis. While NK cells, CD4 + and CD8 + T cells, dendritic cells (DC) and pro-inflammatory M1 macrophages promote anti-tumor immune responses, heterogeneous populations of myeloid-derived suppressor cells (MDSC), FOXP3 + regulatory T cells and M2 macrophages counteract tumor immunity [ 23 , 31 ]. The complexity of the immune system is reflected by the homing of immune cells, the composition of the immune cell infiltrate, the amount of inflammation and frequency of TILs, which affect the overall survival (OS) of patients and the efficacy of (immuno)therapy.…”

The Role of the RNA-Binding Protein Family MEX-3 in Tumorigenesis

“…In the literature, it was already reported that MEX-3B expression leads to a downregulation of HLA-A, thereby inhibiting cancer immunotherapy of anti-PD-1-treated melanoma patients [ 35 ]. In melanoma, different immune evasion strategies were reported, which under physiological conditions contribute to the functional immune-privileged tissue microenvironment, including the downregulation of HLA-Ia surface levels, reduced expression of antigen processing machinery (APM) components, as well as induced expression or secretion of immunomodulatory ligands like HLA-G, HLA-E, PD-L1, TGF-β, and IL-10 [ 58 , 59 , 60 , 61 ].…”