Follicular Lymphoma Microenvironment Characteristics Associated with Tumor Cell Mutations and MHC Class II Expression.

Autor:	Han G; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas., Deng Q; Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, Texas., Marques-Piubelli ML; Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas., Dai E; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas., Dang M; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas., Ma MCJ; Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, Texas., Li X; Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, Texas., Yang H; Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, Texas., Henderson J; Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, Texas., Kudryashova O; BostonGene Corporation, Waltham, Massachusetts., Meerson M; BostonGene Corporation, Waltham, Massachusetts., Isaev S; BostonGene Corporation, Waltham, Massachusetts., Kotlov N; BostonGene Corporation, Waltham, Massachusetts., Nomie KJ; BostonGene Corporation, Waltham, Massachusetts., Bagaev A; BostonGene Corporation, Waltham, Massachusetts., Parra ER; Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas., Solis Soto LM; Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas., Parmar S; Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, Texas., Hagemeister FB; Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, Texas., Ahmed S; Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, Texas., Iyer SP; Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, Texas., Samaniego F; Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, Texas., Steiner R; Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, Texas., Fayad L; Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, Texas., Lee H; Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, Texas., Fowler NH; Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, Texas.; BostonGene Corporation, Waltham, Massachusetts., Flowers CR; Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, Texas., Strati P; Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, Texas., Westin JR; Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, Texas., Neelapu SS; Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, Texas., Nastoupil LJ; Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, Texas., Vega F; Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas., Wang L; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas.; UTHealth Graduate School of Biomedical Sciences, The University of Texas MD Anderson Cancer Center, Houston, Texas., Green MR; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas.; Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, Texas.; UTHealth Graduate School of Biomedical Sciences, The University of Texas MD Anderson Cancer Center, Houston, Texas.; Center for Cancer Epigenetics, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Jazyk:	angličtina
Zdroj:	Blood cancer discovery [Blood Cancer Discov] 2022 Sep 06; Vol. 3 (5), pp. 428-443.
DOI:	10.1158/2643-3230.BCD-21-0075
Abstrakt:	Follicular lymphoma (FL) is a B-cell malignancy with a complex tumor microenvironment that is rich in nonmalignant immune cells. We applied single-cell RNA sequencing to characterize the diverse tumor and immune cell populations of FL and identified major phenotypic subsets of FL T cells, including a cytotoxic CD4 T-cell population. We characterized four major FL subtypes with differential representation or relative depletion of distinct T-cell subsets. By integrating exome sequencing, we observed that somatic mutations are associated with, but not definitive for, reduced MHC expression on FL cells. In turn, expression of MHCII genes by FL cells was associated with significant differences in the proportions and targetable immunophenotypic characteristics of T cells. This provides a classification framework of the FL microenvironment in association with FL genotypes and MHC expression, and informs different potential immunotherapeutic strategies based upon tumor cell MHCII expression. Significance: We have characterized the FL-infiltrating T cells, identified cytotoxic CD4 T cells as an important component that is associated with tumor cell-intrinsic characteristics, and identified sets of targetable immune checkpoints on T cells that differed from FLs with normal versus low MHC expression. See related commentary by Melnick, p. 374. This article is highlighted in the In This Issue feature, p. 369. (©2022 The Authors; Published by the American Association for Cancer Research.)
Databáze:	MEDLINE
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