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

Follicular lymphoma (FL) is a B-cell malignancy with a complex tumor microen-vironment 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 identifi ed 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 defi ni-tive for, reduced MHC expression on FL cells. In turn, expression of MHCII genes by FL cells was associ-ated with signifi cant differences in the proportions and targetable immunophenotypic characteristics of T cells. This provides a classifi cation 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-infi ltrating T cells, identifi ed cytotoxic CD4 T cells as an important component that is associated with tumor cell-intrinsic characteristics, and identifi ed sets of targetable immune checkpoints on T cells that differed from FLs with normal versus low MHC expression.