Resident memory CD8 T cells exist in high grade sarcomas
Jichang Han2, Jodi Wilkowski1, Wei Jiang1, Christina Angeles1
1Surgery, University of Michigan, Ann Arbor, Michigan, United States, 2Microbiology and Immunology, The Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, United States
Objective: While surgical resection is the most effective treatment option for retroperitoneal sarcoma, patients have a high risk of recurrence and cytotoxic chemotherapy has poor response rates. Immunotherapy has shown tremendous efficacy in solid tumors, however, there have been few studies in sarcoma. In order to discover new immunotherapeutic approaches, there is an urgent need to understand the sarcoma tumor microenvironment (TME). Design: Descriptive study of the infiltration levels and phenotypes of tumor infiltrating lymphocytes (TILs) among different subtypes of sarcoma. Flow cytometry was performed using antibodies for T cells (CD45, CD3, CD4, CD8) and phenotypic markers (CD69, CD62L, CD103, CD49a, PD1, TIM3). Setting: Cancer center. Patients: 8 patients with retroperitoneal sarcoma: 3 well-differentiated liposarcoma (WDLPS), 1 dedifferentiated liposarcoma (DDLPS), 2 WDLPS/DDLPS and 2 leiomyosarcoma. Interventions: None. Main Outcome Measure(s): Differences in overall immune infiltrate and T cell populations among subtypes of sarcoma. Results: CD8+ T cells in DDLPS were comprised of both circulating effector memory (TEM) and resident memory (TRM) CD8+ cells, while WDLPS had mostly TEM cells. CD8+ T cells in leiomyosarcoma had a similar phenotype as DDLPS. In 2 patients with WDLPS/DDLPS, WDLPS tumors had lower levels of TILs compared to DDLPS. Phenotypic analysis showed that TRM cells in DDLPS are PD1+ TIM3-, exhibiting a feature of activation but not terminal exhaustion. TEM cells in WDLPS also expressed PD1 but at a lower proportion compared to the TRM cells. Conclusions: These results show that while clinically more aggressive, the higher histologic grade sarcomas, DDLPS and leiomyosarcoma, had higher levels of TILs along with the presence of TRM cells compared to the low grade WDLPS. These findings indicate potential promising targets for immunotherapy.
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