Characterization of innate lymphoid cell subsets infiltrating melanoma and epithelial ovarian tumors

Oncoimmunology. 2024 May 10;13(1):2349347. doi: 10.1080/2162402X.2024.2349347. eCollection 2024.

Abstract

The innate lymphoid cell (ILC) family is composed of heterogeneous innate effector and helper immune cells that preferentially reside in tissues where they promote tissue homeostasis. In cancer, they have been implicated in driving both pro- and anti-tumor responses. This apparent dichotomy highlights the need to better understand differences in the ILC composition and phenotype within different tumor types that could drive seemingly opposite anti-tumor responses. Here, we characterized the frequency and phenotype of various ILC subsets in melanoma metastases and primary epithelial ovarian tumors. We observed high PD-1 expression on ILC subsets isolated from epithelial ovarian tumor samples, while ILC populations in melanoma samples express higher levels of LAG-3. In addition, we found that the frequency of cytotoxic ILCs and NKp46+ILC3 in tumors positively correlates with monocytic cells and conventional type 2 dendritic cells, revealing potentially new interconnected immune cell subsets in the tumor microenvironment. Consequently, these observations may have direct relevance to tumor microenvironment composition and how ILC subset may influence anti-tumor immunity.

Keywords: Epithelial ovarian cancer; LAG-3; NK cells; PD-1; T cells; innate lymphoid cells; melanoma; myeloid cells.

MeSH terms

  • Antigens, CD / metabolism
  • Carcinoma, Ovarian Epithelial* / immunology
  • Carcinoma, Ovarian Epithelial* / pathology
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Dendritic Cells / pathology
  • Female
  • Humans
  • Immunity, Innate*
  • Lymphocyte Activation Gene 3 Protein
  • Lymphocyte Subsets / immunology
  • Lymphocyte Subsets / metabolism
  • Lymphocytes, Tumor-Infiltrating* / immunology
  • Melanoma* / immunology
  • Melanoma* / pathology
  • Natural Cytotoxicity Triggering Receptor 1 / metabolism
  • Neoplasms, Glandular and Epithelial / immunology
  • Neoplasms, Glandular and Epithelial / pathology
  • Ovarian Neoplasms* / immunology
  • Ovarian Neoplasms* / pathology
  • Programmed Cell Death 1 Receptor / metabolism
  • Tumor Microenvironment / immunology

Grants and funding

This work was supported by a CIHR foundation award (CIHR FDN #143220 to PSO), a CHIR operating grant (to PSO), the Wolfond Immunotherapy Fund (to PSO), the Alberta Cancer Foundation/Arnie Charbonneau Cancer Institute laboratory start-up package (to NJ), a Canadian Cancer Society Emerging Scholar Research Grant (grant #708072 to NJ), and the Dr. Robert C. Westbury Fund for Melanoma Research (to NJ). The results published here are in part based upon data generated by the TCGA Research Network (https://www.cancer.gov/tcga/).