Characterization of immune exhaustion and suppression in the tumor microenvironment of splenic marginal zone lymphoma

Theodora Anagnostou, Zhi Zhang Yang, Shahrzad Jalali, Hyo Jin Kim, Daniel P. Larson, Xinyi Tang, Yue Yu, Joshua C. Pritchett, Jose Villasboas Bisneto, Tammy L. Price-Troska, Patrizia Mondello, Anne J. Novak, Stephen M. Ansell

Research output: Contribution to journalArticlepeer-review


The role of the tumor microenvironment (TME) and intratumoral T cells in splenic marginal zone lymphoma (sMZL) is largely unknown. In the present study, we evaluated 36 sMZL spleen specimens by single cell analysis to gain a better understanding of the TME in sMZL. Using mass cytometry (CyTOF), we observed that the TME in sMZL is distinct from that of control non-malignant reactive spleen (rSP). We found that the number of TFH cells varied greatly in sMZL, ICOS+ TFH cells were more abundant in sMZL than rSP, and TFH cells positively correlated with increased numbers of memory B cells. Treg cell analysis revealed that TIGIT+ Treg cells are enriched in sMZL and correlate with suppression of TH17 and TH22 cells. Intratumoral CD8+ T cells were comprised of subsets of short-lived, exhausted and late-stage differentiated cells, thereby functionally impaired. We observed that T-cell exhaustion was present in sMZL and TIM-3 expression on PD-1low cells identified cells with severe immune dysfunction. Gene expression profiling by CITE-seq analysis validated this finding. Taken together, our data suggest that the TME as a whole, and T-cell population specifically, are heterogenous in sMZL and immune exhaustion is one of the major factors impairing T-cell function.

Original languageEnglish (US)
Pages (from-to)1485-1498
Number of pages14
Issue number7
StatePublished - Jul 2023

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research


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