4.7 Review

The importance of immune checkpoints in immune monitoring: A future paradigm shift in the treatment of cancer

Journal

BIOMEDICINE & PHARMACOTHERAPY
Volume 146, Issue -, Pages -

Publisher

ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.biopha.2021.112516

Keywords

Immune checkpoints; Immune checkpoint inhibitors; miRNAs; Immunotherapy

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The growth and development of cancer are directly correlated to the suppression of the immune system, with immune checkpoints playing a key role in inhibiting anti-tumor immune responses. Up-regulation of inhibitory immune checkpoints on immune cells during tumor progression suppresses anti-tumor immune responses and promotes immune escape. Targeting inhibitory immune checkpoints through antibodies or miRNAs is a promising therapeutic strategy, and immune checkpoint inhibitors have shown favorable results in enhancing immune cell-induced antitumor responses.
The growth and development of cancer are directly correlated to the suppression of the immune system. A major breakthrough in cancer immunotherapy depends on various mechanisms to detect immunosuppressive factors that inhibit anti-tumor immune responses. Immune checkpoints are expressed on many immune cells such as T-cells, regulatory B cells (Bregs), dendritic cells (DCs), natural killer cells (NKs), regulatory T (Tregs), M2-type macrophages, and myeloid-derived suppressor cells (MDSCs). Immune inhibitory molecules, including CTLA-4, TIM-3, TIGIT, PD-1, and LAG-3, normally inhibit immune responses via negatively regulating immune cell signaling pathways to prevent immune injury. However, the up-regulation of inhibitory immune checkpoints during tumor progression on immune cells suppresses anti-tumor immune responses and promotes immune escape in cancer. It has recently been indicated that cancer cells can up-regulate various pathways of the immune checkpoints. Therefore, targeting immune inhibitory molecules through antibodies or miRNAs is a promising therapeutic strategy and shows favorable results. Immune checkpoint inhibitors (ICIs) are introduced as a new immunotherapy strategy that enhance immune cell-induced antitumor responses in many patients. In this re-view, we highlighted the function of each immune checkpoint on different immune cells and therapeutic stra-tegies aimed at using monoclonal antibodies and miRNAs against inhibitory receptors. We also discussed current challenges and future strategies for maximizing these FDA-approved immunosuppressants' effectiveness and clinical success in cancer treatment.

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