To decouple the immune landscape of tumors from that of general inflammatory responses, Mair and Erickson et al. sequenced patient HNSCC samples alongside non-malignant but inflamed oral mucosa (OM) and blood. Broadly, immune composition and phenotype were consistent between HNSCC and OM, both different from blood; however, more Tregs, fewer cDC1s, and altered DC3 (mregDCs) transcriptomes were noted in HNSCC versus OM. Particularly, an IL1R1+ Treg population expressing ICOS and CTLA-4, with distinct gene expression and unique suppressive capacity was found in HNSCC, with IL1R1 inducible on Tregs through TCR stimulation.
Contributed by Alex Najibi
ABSTRACT: Immunotherapies have achieved remarkable successes in the treatment of cancer, but major challenges remain(1,2). 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 treatment(3,4). 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 (T(reg)) 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(+) T(reg) cells had responded to antigen recently and demonstrate that they are clonally expanded with superior suppressive function compared with IL1R1(-) T(reg) 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.
Author Info: (1) Fred Hutchinson Cancer Research Center, Vaccine and Infectious Disease Division, Seattle, WA, USA. (2) Fred Hutchinson Cancer Research Center, Vaccine and Infectious Disease Di
Author Info: (1) Fred Hutchinson Cancer Research Center, Vaccine and Infectious Disease Division, Seattle, WA, USA. (2) Fred Hutchinson Cancer Research Center, Vaccine and Infectious Disease Division, Seattle, WA, USA. Department of Immunology, University of Washington, Seattle, WA, USA. (3) Fred Hutchinson Cancer Research Center, Vaccine and Infectious Disease Division, Seattle, WA, USA. (4) Fred Hutchinson Cancer Research Center, Vaccine and Infectious Disease Division, Seattle, WA, USA. Department of Immunology, University of Washington, Seattle, WA, USA. (5) Fred Hutchinson Cancer Research Center, Vaccine and Infectious Disease Division, Seattle, WA, USA. (6) Fred Hutchinson Cancer Research Center, Vaccine and Infectious Disease Division, Seattle, WA, USA. Cape Town HVTN Immunology Laboratory, Hutchinson Centre Research Institute of South Africa, NPC (HCRISA), Cape Town, South Africa. (7) Fred Hutchinson Cancer Research Center, Vaccine and Infectious Disease Division, Seattle, WA, USA. Molecular and Cellular Biology Graduate Program, University of Washington, Seattle, WA, USA. (8) Department of Immunology, University of Washington, Seattle, WA, USA. Fred Hutchinson Cancer Research Center, Clinical Research Division, Seattle, WA, USA. (9) Department of Periodontics, School of Dentistry, University of Washington, Seattle, WA, USA. Department of Periodontics, University of Tennessee Health Science Center, College of Dentistry, Memphis, TN, USA. (10) Department of Otolaryngology-Head and Neck Surgery, University of Washington, Seattle, WA, USA. (11) Fred Hutchinson Cancer Research Center, Vaccine and Infectious Disease Division, Seattle, WA, USA. Department of Statistics, University of Washington, Seattle, WA, USA. University of Lausanne and Lausanne University Hospital, Switzerland, Lausanne, Switzerland. (12) Fred Hutchinson Cancer Research Center, Vaccine and Infectious Disease Division, Seattle, WA, USA. mprlic@fredhutch.org. Department of Global Health, University of Washington, Seattle, WA, USA. mprlic@fredhutch.org.
