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

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
• innate lymphoid cells
• LAG-3
• melanoma
• myeloid cells
• NK cells
• PD-1
• T cells

Acknowledgment

We thank the members of the Ohashi and Jacquelot laboratories for their insightful comments and discussion. We thank Dr. Heewon Seo for his help with the TCGA analysis and correlation plots. We thank Dr. Danny Ghazarian for his help with sample collection. We thank the Princess Margaret Cancer Centre flow facility for their technical support.

Disclosure statement

Dr. Pamela Ohashi is on Scientific Advisory Boards for Providence Therapeutics, Treadwell Therapeutics, Tikva Allocell and Rondo Therapeutics. Inc. Dr. Ohashi holds a sponsored research agreement with Providence Therapeutics. No potential conflict of interest was reported by the other authors.

Data availability statement

The authors confirm that the data supporting the findings of this study are available within the article and its supplementary materials.

Authors’ contributions

DCC, MG, KW, AS performed the experiments, participated in data analysis and interpretation, reviewed and edited the manuscript; SDS, MQB, BAC, PAS, MOB, AE, BXW, LN provided patient samples and clinical information, reviewed and edited the manuscript; SM participated in the bioinformatics analysis and interpretation, reviewed and edited the manuscript. PSO participated in data analysis and interpretation, reviewed and edited the manuscript, provided funding and supervision; NJ performed data analysis and interpretation, provided funding and supervision, wrote the initial draft, reviewed and edited the manuscript.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/2162402X.2024.2349347

Additional information

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/).