Targeting the Tumor Microenvironment for Improving Therapeutic Effectiveness in Cancer Immunotherapy: Focusing on Immune Checkpoint Inhibitors and Combination Therapies
Journal
Cancers
Journal Volume
13
Journal Issue
6
Pages
1 - 14
Date Issued
2021-03-10
Author(s)
Abstract
Immune checkpoints play critical roles in the regulation of T-cell effector function, and the effectiveness of their inhibitors in cancer therapy has been established. Immune checkpoint inhibitors (ICIs) constitute a paradigm shift in cancer therapy in general and cancer immunotherapy in particular. Immunotherapy has been indicated to reinvigorate antitumor T-cell activity and dynamically modulate anticancer immune responses. However, despite the promising results in the use of immunotherapy in some cancers, numerous patients do not respond to ICIs without the existence of a clear predictive biomarker. Overall, immunotherapy involves a certain degree of uncertainty and complexity. Research on the exploration of cellular and molecular factors within the tumor microenvironment (TME) aims to identify possible mechanisms of immunotherapy resistance, as well as to develop novel combination strategies involving the specific targeting of the TME for cancer immunotherapy. The combination of this approach with other types of treatment, including immune checkpoint blockade therapy involving multiple agents, most of the responses and effects in cancer therapy could be significantly enhanced, but the appropriate combinations have yet to be established. Moreover, the in-depth exploration of complexity within the TME allows for the exploration of pathways of immune dysfunction. It may also aid in the identification of new therapeutic targets. This paper reviews recent advances in the improvement of therapeutic efficacy on the immune context of the TME and highlights its contribution to cancer immunotherapy.
Subjects
T cell dysfunction; cancer immunotherapy; immune checkpoint; tumor microenvironment
SDGs
Other Subjects
atezolizumab; avelumab; bevacizumab; cancer vaccine; cytotoxic T lymphocyte antigen 4; durvalumab; immune checkpoint inhibitor; ipilimumab; nivolumab; pembrolizumab; placebo; probiotic agent; programmed death 1 ligand 1; programmed death 1 receptor; ticilimumab; vasculotropin; adoptive immunotherapy; cancer immunotherapy; cancer resistance; colorectal tumor; combination drug therapy; drug efficacy; fecal microbiota transplantation; human; intestine flora; melanoma; metastatic melanoma; monotherapy; non small cell lung cancer; nonhuman; overall survival; progression free survival; radioimmunotherapy; renal cell carcinoma; Review; solid malignant neoplasm; tumor associated leukocyte; tumor microenvironment; tumor vascularization; tumor-associated macrophage
Type
review