TY - JOUR
T1 - Cancer immunotherapy by blocking immune checkpoints on innate lymphocytes
AU - Pesce, Silvia
AU - Trabanelli, Sara
AU - Di Vito, Clara
AU - Greppi, Marco
AU - Obino, Valentina
AU - Guolo, Fabio
AU - Minetto, Paola
AU - Bozzo, Matteo
AU - Calvi, Michela
AU - Zaghi, Elisa
AU - Candiani, Simona
AU - Lemoli, Roberto Massimo
AU - Jandus, Camilla
AU - Mavilio, Domenico
AU - Marcenaro, Emanuela
N1 - Funding Information:
pAuubtlhisohreCdovnetrrsiibountioofn ths:e Amllaanuutshcorripstc.ontributed to writing, review, editing, have read and agreed to the published version of the manuscript. Funding: This work was supported by grants from Compagnia di San Paolo (2019.866) to RML, EM, SC, SP, MG, VO, FG, PM; Fondazione Associazione Italiana per la Ricerca sul Cancro (AIRC 5 × 1000-21147 and AIRC IG) to VO, FG, PM; Fondazione Associazione Italiana per la Ricerca sul Cancro (AIRC 5 × 1000-21147 and AIRC IG) to EM, SC, SP, MG, VO; ROCHE 2017 to SP, EM, the Swiss National Science Foundation (PRIMA PR00P3_179727) CJ, the Swiss Cancer League (KFS-4402-02-2018) to CJ, the Helmut Horten Stiftung Foundation to CJ, Fondazione FCoanrdipalzoio(n2e0 1C5a/0r6ip0l3o) t(o20D15M/0,6F0o3n) dtoazDioMne, FAosnsdocaizaizoinoen eAIstsaolicaianzaiopneer lIataRliiacneracapesrullaCRaniccerroca(IGsu2l 0C1a8n-2cr1o56(7IG) to20D1M8-, and Intramural Research Funding of Istituto Clinico Humanitas to DM. EZ was a recipient of fellowships from the Associazione Italiana per la Ricerca sul Cancro (2018-20870, 2020-24051). CDV was a recipient of the post-doctoral fellowships from the Fondazione Umberto Veronesi (2017-1464, 2018-1974, 2019-2563). recipient of the post-doctoral fellowships from the Fondazione Umberto Veronesi (2017-1464, 2018-1974, 2019- 2Conflicts563). of Interest: The authors declare no conflict of interest.
Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/12
Y1 - 2020/12
N2 - 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.
AB - 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.
KW - Immune checkpoint
KW - Immune escape
KW - Immunotherapy
KW - Innate immunity
KW - Innate lymphoid cells
KW - KIR
KW - MiRNA
KW - Natural killer cells
KW - NKG2A
KW - PD-1
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U2 - 10.3390/cancers12123504
DO - 10.3390/cancers12123504
M3 - Review article
AN - SCOPUS:85096635164
VL - 12
SP - 1
EP - 25
JO - Cancers
JF - Cancers
SN - 2072-6694
IS - 12
M1 - 3504
ER -