T-cell phenotype including CD57+ T follicular helper cells in the tumor microenvironment correlate with a poor outcome in follicular lymphoma

• Published in: Blood cancer journal (New York) Vol. 13; no. 1; pp. 124 - 14
• Main Authors: Yang, Zhi-Zhang, Kim, Hyo Jin, Wu, Hongyan, Tang, Xinyi, Yu, Yue, Krull, Jordan, Larson, Daniel P., Moore, Raymond M., Maurer, Matthew J., Pavelko, Kevin D., Jalali, Shahrzad, Pritchett, Joshua C., Mudappathi, Rekha, Wang, Junwen, Villasboas, Jose C., Mondello, Patrizia, Novak, Anne J., Ansell, Stephen M.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 18.08.2023; Springer Nature B.V; Nature Publishing Group
• Subjects: 631/250/580; 692/699/1541/1990/291/1621/1915; Biomedical and Life Sciences; Biomedicine; Cancer Research; Cell Differentiation; Genotype & phenotype; Hematology; Humans; Lymphoma; Lymphoma, Follicular; Oncology; Patients; Phenotype; T Follicular Helper Cells; Tumor Microenvironment
• ISSN: 2044-5385; 2044-5385
• DOI: 10.1038/s41408-023-00899-3

T-lymphocytes are prevalent in the tumor microenvironment of follicular lymphoma (FL). However, the phenotype of T-cells may vary, and the prevalence of certain T-cell subsets may influence tumor biology and patient survival. We therefore analyzed a cohort of 82 FL patients using CyTOF to determine whether specific T-cell phenotypes were associated with distinct tumor microenvironments and patient outcome. We identified four immune subgroups with differing T-cell phenotypes and the prevalence of certain T-cell subsets was associated with patient survival. Patients with increased T cells with early differentiation stage tended to have a significantly better survival than patients with increased T-cells of late differentiation stage. Specifically, CD57 + T FH cells, with a late-stage differentiation phenotype, were significantly more abundant in FL patients who had early disease progression and therefore correlated with an inferior survival. Single cell analysis (CITE-seq) revealed that CD57 + T FH cells exhibited a substantially different transcriptome from CD57 − T FH cells with upregulation of inflammatory pathways, evidence of immune exhaustion and susceptibility to apoptosis. Taken together, our results show that different tumor microenvironments among FL patients are associated with variable T-cell phenotypes and an increased prevalence of CD57 + T FH cells is associated with poor patient survival.