A novel population of CD103-expressing CD56 +regulatory ILCs suppresses intratumoural T cells and are associated with poor prognosis in patients with ovarian carcinoma

Abstract Regulatory innate lymphoid cells (ILCregs) are an emerging family of immunoregulatory cells that suppress innate and adaptive immunity in the context of diseases, including cancer. However, there is currently a lack of lineage-defining surface markers or transcription factors (TFs) that dis...

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Published in:	The Journal of immunology (1950) Vol. 210; no. 1_Supplement; pp. 172 - 172.16
Main Authors:	Chung, Douglas, Vakharia, Jehan, Warner, Kathrin, Jacquelot, Nicolas, Sayad, Azin, Han, SeongJun, Ghaedi, Maryam, Garcia-Batres, Carlos, Elford, Alisha R, Matthews, Jessica A, Wang, Ben X, Nguyen, Linh T, Shaw, Patricia A, Clarke, Blaise A, Bernardini, Marcus Q, Ferguson, Sarah E, Crome, Sarah Q, Ohashi, Pamela S
Format:	Journal Article
Language:	English
Published:	01-05-2023
Online Access:	Get full text
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Summary:	Abstract Regulatory innate lymphoid cells (ILCregs) are an emerging family of immunoregulatory cells that suppress innate and adaptive immunity in the context of diseases, including cancer. However, there is currently a lack of lineage-defining surface markers or transcription factors (TFs) that distinguishes ILCregs from other subsets of ILCs. Moreover, the functional role of ILCregs within the tumour microenvironment (TME) has not been well established. In this study, we uncovered a novel population of CD103-expressing CD56 +ILCregs within the TME that correlated with poor recurrent-free survival (RFS) in patients with epithelial ovarian carcinoma (EOC). CD103 +ILCregs expressed distinct surface markers and TFs that distinguishes them from canonical CD56 +natural killer (NK) cells. Moreover, intratumoural CD103 +ILCregs expressed markers (i.e., CD39, CD69, CD101, TIGIT) and transcriptomic profiles that are shared with Tregs, suggesting that they may have immunoregulatory properties. We found that ascites-derived TGF-β drives NK cell conversion into CD103 +ILCs that can suppress autologous CD4 +T cells in vitro. Furthermore, intratumoural CD103 +ILCregs suppressed autologous CD8 +T cells in vitro. Finally, we found that the abundance of CD103 +ILCregs in the TME were associated with reduced levels of both activated CD4 +T cells and CD8 +T cells. Overall, we have identified CD103 +ILCregs as distinct immunoregulatory cells that suppresses T cells within the TME of patients with EOC. Further untangling of the complex networks of immune regulation, including ILCregs, may give rise to novel therapeutic targets to enhance anti-tumour immunity and improve clinical response rates to immunotherapies. This work was supported by a CIHR foundation award (CIHR FDN #143220), a TRANSCAN CIHR grant (CIHR – TRN #184713), a TRI grant from the Ontario Institute for Cancer Research (TRI OICR GCS #108796), and the Terry Fox Research Institute (TFRI-iTNT #1060). This project was also generously funded in memory of Mr. JIM JoTak under the Canadian Cancer Society (CCSRI #706152).
ISSN:	0022-1767 1550-6606
DOI:	10.4049/jimmunol.210.Supp.172.16