Data on T-cell Exhaustion Support Earlier Use of T-cell-based Therapies in Splenic MZL

By Leah Lawrence - Last Updated: September 10, 2023

The composition of T cells in patients with splenic marginal zone lymphoma (sMZL) may affect the efficacy of T-cell-based therapies, according to a poster presented at the Eleventh Annual Meeting of the Society of Hematologic Oncology.

Theodora Anagnostou, MD, of the Icahn School of Medicine at Mount Sinai in New York and colleagues presented findings from a retrospective analysis of pretreatment T-cell samples taken from patients with sMZL treated at Mayo Clinic.

Using a single-cell immunophenotypic approach based on CyTOF and CITEseq, the researchers analyzed the T cells from 36 sMZL spleen specimens and compared them with healthy spleen controls. They attempted to correlate the levels of different T-cell subsets with clinical outcomes.

The analysis showed that the levels of T-follicular helper (TFH) cells correlated with higher numbers of memory B cells, which suggested involvement of inducible T-cell costimulatory-positive TFH cells in the regulation of lymphoma cell differentiation.

Additionally, TIGIT-positive T regulatory cells were enriched in sMZL and correlated with the suppression of TH17 and TH22 cells.

Intratumoral CD8 cells were compromised of short-lived, exhausted, and late-stage differentiated cells, indicating they are functionally impaired, according to the researchers. These terminally differentiated CD8 levels correlated with inferior event-free survival.

Phenotypes of early differentiation correlated with better overall survival; in contrast, expression of markers of late differentiation correlated with worse overall survival.

According to the researchers, these data “suggest that immune exhaustion is one of the major factors impairing T-cell function in sMZL” and “highlight the importance of maintaining health T-cell pools as a predictor of long-term disease-free intervals.”


Anagnostou T, Yang Z-Z, Jalali S, et al. Signatures of immune exhaustion and suppression in the tumor microenvironment of splenic marginal zone lymphoma correlate with inferior clinical outcomes. Abstract IBCL-270. Presented Eleventh Annual Meeting of the Society of Hematologic Oncology; September 6-9, 2023; Houston, Texas.

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