Immune microenvironment subtypes and association with tumor cell mutations and antigen expression in follicular lymphoma
Year: 2021
Type: preprint
Study design: Observational Study
Abstract: Follicular lymphoma (FL) is a B-cell lymphoma with a complex tumor microenvironment that is rich in non-malignant 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 novel cytotoxic CD4 T-cell population. Their relative proportions of T-cells defined four major FL subtypes, characterized by 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 antigen presentation on FL cells. In turn, expression of MHC class II genes by FL cells was associated with significant differences in the proportions and targetable immunophenotypic characteristics. This provides a classification framework of the FL microenvironment, their association with FL genotypes and antigen presentation, and informs different potential immunotherapeutic strategies based upon tumor cell MHC class II expression. Statement of significance We have characterized the FL-infiltrating T-cells, identified cytotoxic CD4 T-cells as an important component, showed that the abundance of these T-cell populations is associated with tumor-cell-intrinsic characteristics, and identified sets of targetable immune checkpoints on T-cells that differed between FLs with normal versus low antigen presentation.
Authors: Guangchun Han, Qing Deng, Enyu Dai, Minghao Dang, John Ma, Haopeng Yang, Olga Kudryashova, Mark Meerson, Sergey Isaev, Nikita Kotlov, Krystle Nomie, Alexander Bagaev, Simrit Parmar, Fredrick Hagemeister, Sairah Ahmed, Swami Iyer, Filepe Samaniego, Raphael Steiner, Luis Fayad, Hun Lee, Nathan Fowler, Francisco Vega, Christopher R. Flowers, Paolo Strati, Jason R. Westin, Sattva S. Neelapu, Loretta J. Nastoupil, Linghua Wang, Michael R. Green
Language: English
Subfield: Pathology and Forensic Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: G1468253849, G293715275, G4731506331
OpenAlex ID: W3157637801