Follicular Lymphoma Microenvironment Characteristics Associated with Tumor Cell Mutations and MHC Class II Expression
Guangchun Han, Qing Deng, Mario L. Marques-Piubelli, Enyu Dai, Minghao Dang, Man Chun John Ma, Xubin Li, Haopeng Yang, Jared Henderson, Olga Kudryashova, Mark Meerson, Sergey Isaev, Nikita Kotlov, Krystle J. Nomie, Alexander Bagaev, Edwin R. Parra, Luisa M. Solis Soto, Simrit Parmar, Fredrick B. Hagemeister, Sairah Ahmed, Swaminathan P. Iyer, Felipe Samaniego, Raphael Steiner, Luis Fayad, Hun Lee, Nathan H. Fowler, Christopher R. Flowers, Paolo Strati, Jason R. Westin, Sattva S. Neelapu, Loretta J. Nastoupil, Francisco Vega, Linghua Wang, Michael R. Green
Abstract
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.
Datasets
1. Single cell RNA sequencing of follicular lymphoma
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Source data
https://cellxgene.cziscience.com/collections/968834a0-1895-40df-8720-666029b3bbac
Alias names
EGAS00001006052, PMID35687817, PMC9894575
Cite this study
Han, G., Deng, Q., Marques-Piubelli, M.L., Dai, E., Dang, M., Ma, M.C.J., Li, X., Yang, H., Henderson, J., Kudryashova, O. and Meerson, M., 2022. Follicular lymphoma microenvironment characteristics associated with tumor cell mutations and MHC class II expression. Blood cancer discovery, 3(5), pp.428-443. https://doi.org/10.1158/2643-3230.BCD-21-0075