Differential responses of peripheral and tumor-infiltrating T cells to immunotherapy in patients

Soft tissue sarcomas (STSs) are a group of rare cancer types and advanced and/or metastatic STSs usually have a poor prognosis. Oncostatin M (OSM) is a pleiotropic cytokine with promising antitumoral properties. However, it has been reported that OSM can promote both pro- and anti-tumorigenic events in the tumor microenvironment (TME) and it is fairly unknown which factors drive these events. This study aimed to analyze the immunological contextures and in vitro responses to immunotherapy in ten patients with liposarcoma, leiomyosarcoma, and myxofibrosarcoma. The effects of in vitro OSM administration on immune cells isolated from peripheral blood and tumoral tissue from patients and the potential cooperation between OSM and nivolumab were investigated. The study cohort was designed to explore the histology-driven possibilities of therapeutic targeting of STSs. Clinicopathological data of the patients were analyzed and did not significantly correlate with the proportions or phenotypes of TILs and PBMCs. Peripheral CD45+ cell population decreased after the treatments, whereas peripheral CD45- cell population was not significantly influenced by the treatments. However, peripheral CD45- TRAIL-R+ cell population was altered following OSM treatment and significantly increased after the OSM and nivolumab combinatorial treatment. CD4+ and CD8+ cell populations isolated from the peripheral blood showed slight changes. In the tumoral tissue, CD8+ TILs and CD45- TRAIL-R+ cell populations were boosted by nivolumab and significantly enriched by OSM. This data suggests that OSM may play a role in the treatment of leiomyosarcoma, myxofibrosarcoma, and liposarcoma. In conclusion, the biological efficacy of OSM is reflected in the TME rather that in the peripheral blood of patients in this study cohort. In some cases, nivolumab may potentiate its mechanism of action. Nonetheless, additional histotype-tailored studies are needed to fully understand the functions of OSM in STSs.