Sarcoma
Alicia A. Gingrich, MD, MS
General Surgery Chief Resident
University of California Davis
Sacramento, California, United States
Disclosure: Disclosure information not submitted.
Despite the success of immunotherapy, there is an unmet need for efficacious agents for soft tissue sarcoma (STS). We sought to characterize the frequency and phenotype of blood and tumor infiltrating lymphocytes (TILs) in STS, including expression of the NK and T cell exhaustion marker TIGIT, with the goal of identifying targets for immunotherapy approaches.
Methods:
From 2018 – 2021, we prospectively analyzed blood and fresh STS tumor specimens for flow cytometric immune phenotype from patients undergoing surgery. We determined frequencies of TILs as well as TIGIT expression on T cells (CD3+) and NK cells (CD3-CD56+) in tumor samples and matched peripheral blood. Correlations between TIL populations, TIGIT expression, and disease recurrence free survival (DRFS) were then calculated using log-rank test and Kaplan Meier curves.
Results:
Among our prospective cohort of 26 patients, 50% of tumors were located on the extremity/trunk and 50% in the retroperitoneum. Average age at diagnosis was 56.6 years, and 61% were men. Most common histologic subtypes were dedifferentiated liposarcoma (23%) and leiomyosarcoma (15%). Average tumor size at resection of 17.9 cm (2.5 - 60cm). All patients had high-grade histology. Median follow up was 16.2 months, median DRFS was 14.6 months, and overall survival was 88%. High CD3+ T cell tumor infiltrate was associated with improved DRFS (p = 0.0236), whereas high NK cells were not (p = 0.7289). Patients with low TIGIT expression in CD3+ TILs had fewer DR events during follow up than those with high expression. This was not seen in the T cells from peripheral blood. Patients with low TIGIT expression in NK cells from peripheral blood had fewer DR events than those with high expression, although this difference was not statistically significant.
Conclusions:
Intratumoral T cells are associated with improved disease recurrence free survival in STS. There is a decreased frequency of DR events with low TIGIT expression for CD3+ TILs and peripheral blood NK cells. Our data suggest TIGIT expression may serve as a biomarker of prognosis and target to augment immune response in STS patients via novel immune checkpoint inhibitory pathways.