Microbiota and plasticity of antigen-presenting ILC3s: impact on antitumor immune response

Gut Microbes. 2024 Jan-Dec;16(1):2390135. doi: 10.1080/19490976.2024.2390135. Epub 2024 Aug 19.

Abstract

Growing evidence highlights the pivotal role of RORγt-innate lymphoid cells (ILCs) in the establishment of antitumor immune response and in enhancing tumor sensitivity to immunotherapy. Noteworthy, type 3 ILCs (ILC3s) have been recently acknowledged as an important class of antigen-presenting cells (APCs) in the context of host-microorganism interactions shaping the adaptive immune response in the intestinal mucosa. Although a broad range of mouse models has led to significant progress in untangling the role of ILC3s as APCs, the outcome of major histocompatibility complex (MHC)-dependent ILC-T cell crosstalk in colorectal cancer (CRC) remains underexplored in human. Moreover, expression of MHCII is confined to ILC3 subset, endowed with lymphoid tissue-inducing properties, that adopts tissue-specific fates and functions. Intestinal microbiota could dictate the plasticity of antigen-presenting ILC3s and we here summarize our current understanding of the functions of these cells in both mouse and human CRC discussing the role of microbiota as a key modulator of their tumor-suppressive activity.

Keywords: CRC; ILC3; antigen presentation; antitumor immunity; human; microbiota; plasticity; tertiary lymphoid organs.

Publication types

  • Review

MeSH terms

  • Animals
  • Antigen-Presenting Cells* / immunology
  • Colorectal Neoplasms* / immunology
  • Colorectal Neoplasms* / microbiology
  • Gastrointestinal Microbiome* / immunology
  • Humans
  • Immunity, Innate
  • Intestinal Mucosa / immunology
  • Intestinal Mucosa / microbiology
  • Lymphocytes* / immunology
  • Mice

Grants and funding

Research in our Laboratories is supported by grants provided by Italian Ministry of Health, “Ricerca Finalizzata 2018” to GF and [PNRR-MAD-2022-12375909] to IB; by Italian Ministry of Education, University and Research (MIUR), “PRIN 2017” and “PRIN 2022” to GF, “PRIN 2022 PNRR to SC and “Finanziamento Annuale Individuale Attività Base di Ricerca FFABR” to IB and PC.