Cancer Immunotherapy by Blocking Immune Checkpoints on Innate Lymphocytes.

Pesce S; Trabanelli S; Di Vito C; Greppi M; Obino V; Guolo F; Minetto P; Bozzo M; Calvi M; Zaghi E; Candiani S; Lemoli RM; Jandus C; Mavilio D; Marcenaro E

doi:10.3390/cancers12123504

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Journal article

Cancer Immunotherapy by Blocking Immune Checkpoints on Innate Lymphocytes.

Pesce S Department of Experimental Medicine (DIMES) and Centre of Excellence for Biomedical Research (CEBR), University of Genova, 16132 Genova, Italy.
Trabanelli S Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, CH-1211 Geneva, Switzerland.
Di Vito C Unit of Clinical and Experimental Immunology, Humanitas Clinical and Research Center, 20089 Rozzano, Milan, Italy.
Greppi M Department of Experimental Medicine (DIMES) and Centre of Excellence for Biomedical Research (CEBR), University of Genova, 16132 Genova, Italy.
Obino V Department of Experimental Medicine (DIMES) and Centre of Excellence for Biomedical Research (CEBR), University of Genova, 16132 Genova, Italy.
Guolo F Clinic of Hematology, Department of Internal Medicine (DIMI), University of Genoa, 16132 Genova, Italy.
Minetto P Clinic of Hematology, Department of Internal Medicine (DIMI), University of Genoa, 16132 Genova, Italy.
Bozzo M Department of Earth, Environment and Life Sciences (DISTAV), University of Genova, 16132 Genova, Italy.
Calvi M Unit of Clinical and Experimental Immunology, Humanitas Clinical and Research Center, 20089 Rozzano, Milan, Italy.
Zaghi E Unit of Clinical and Experimental Immunology, Humanitas Clinical and Research Center, 20089 Rozzano, Milan, Italy.
Candiani S Department of Earth, Environment and Life Sciences (DISTAV), University of Genova, 16132 Genova, Italy.
Lemoli RM Clinic of Hematology, Department of Internal Medicine (DIMI), University of Genoa, 16132 Genova, Italy.
Jandus C Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, CH-1211 Geneva, Switzerland.
Mavilio D Unit of Clinical and Experimental Immunology, Humanitas Clinical and Research Center, 20089 Rozzano, Milan, Italy.
Marcenaro E Department of Experimental Medicine (DIMES) and Centre of Excellence for Biomedical Research (CEBR), University of Genova, 16132 Genova, Italy.

2020-12-01

Published in:

Cancers. - 2020

English Immune checkpoints refer to a plethora of inhibitory pathways of the immune system that play a crucial role in maintaining self-tolerance and in tuning the duration and amplitude of physiological immune responses to minimize collateral tissue damages. The breakdown of this delicate balance leads to pathological conditions, including cancer. Indeed, tumor cells can develop multiple mechanisms to escape from immune system defense, including the activation of immune checkpoint pathways. The development of monoclonal antibodies, targeting inhibitory immune checkpoints, has provided an immense breakthrough in cancer therapy. Immune checkpoint inhibitors (ICI), initially developed to reverse functional exhaustion in T cells, recently emerged as important actors in natural killer (NK)-cell-based immunotherapy. Moreover, the discovery that also helper innate lymphoid cells (ILCs) express inhibitory immune checkpoints, suggests that these molecules might be targeted on ILCs, to modulate their functions in the tumor microenvironment. Recently, other strategies to achieve immune checkpoint blockade have been developed, including miRNA exploiting systems. Herein, we provide an overview of the current knowledge on inhibitory immune checkpoints on NK cells and ILCs and we discuss how to target these innate lymphocytes by ICI in both solid tumors and hematological malignancies.

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