Cancer immunotherapy by blocking immune checkpoints on innate lymphocytes

Silvia Pesce, Sara Trabanelli, Clara Di Vito, Marco Greppi, Valentina Obino, Fabio Guolo, Paola Minetto, Matteo Bozzo, Michela Calvi, Elisa Zaghi, Simona Candiani, Roberto Massimo Lemoli, Camilla Jandus, Domenico Mavilio, Emanuela Marcenaro

Research output: Contribution to journalReview articlepeer-review


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.

Original languageEnglish
Article number3504
Pages (from-to)1-25
Number of pages25
Issue number12
Publication statusPublished - Dec 2020


  • Immune checkpoint
  • Immune escape
  • Immunotherapy
  • Innate immunity
  • Innate lymphoid cells
  • KIR
  • MiRNA
  • Natural killer cells
  • NKG2A
  • PD-1

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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