Extricating human tumour immune alterations from tissue inflammation

Florian Mair, Jami R. Erickson, Marie Frutoso, Andrew J. Konecny, Evan Greene, Valentin Voillet, Nicholas J. Maurice, Anthony Rongvaux, Douglas Dixon, Brittany Barber, Raphael Gottardo and Martin Prlic ()
Additional contact information
Florian Mair: Vaccine and Infectious Disease Division
Jami R. Erickson: Vaccine and Infectious Disease Division
Marie Frutoso: Vaccine and Infectious Disease Division
Andrew J. Konecny: Vaccine and Infectious Disease Division
Evan Greene: Vaccine and Infectious Disease Division
Valentin Voillet: Vaccine and Infectious Disease Division
Nicholas J. Maurice: Vaccine and Infectious Disease Division
Anthony Rongvaux: University of Washington
Douglas Dixon: University of Washington
Brittany Barber: University of Washington
Raphael Gottardo: Vaccine and Infectious Disease Division
Martin Prlic: Vaccine and Infectious Disease Division

Nature, 2022, vol. 605, issue 7911, 728-735

Abstract: Abstract Immunotherapies have achieved remarkable successes in the treatment of cancer, but major challenges remain1,2. An inherent weakness of current treatment approaches is that therapeutically targeted pathways are not restricted to tumours, but are also found in other tissue microenvironments, complicating treatment3,4. Despite great efforts to define inflammatory processes in the tumour microenvironment, the understanding of tumour-unique immune alterations is limited by a knowledge gap regarding the immune cell populations in inflamed human tissues. Here, in an effort to identify such tumour-enriched immune alterations, we used complementary single-cell analysis approaches to interrogate the immune infiltrate in human head and neck squamous cell carcinomas and site-matched non-malignant, inflamed tissues. Our analysis revealed a large overlap in the composition and phenotype of immune cells in tumour and inflamed tissues. Computational analysis identified tumour-enriched immune cell interactions, one of which yields a large population of regulatory T (Treg) cells that is highly enriched in the tumour and uniquely identified among all haematopoietically-derived cells in blood and tissue by co-expression of ICOS and IL-1 receptor type 1 (IL1R1). We provide evidence that these intratumoural IL1R1+ Treg cells had responded to antigen recently and demonstrate that they are clonally expanded with superior suppressive function compared with IL1R1− Treg cells. In addition to identifying extensive immunological congruence between inflamed tissues and tumours as well as tumour-specific changes with direct disease relevance, our work also provides a blueprint for extricating disease-specific changes from general inflammation-associated patterns.

Date: 2022
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DOI: 10.1038/s41586-022-04718-w

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