Impact of Tertiary Lymphoid Structure on Prognosis and Tumor Microenvironment in Undifferentiated Pleomorphic Sarcoma

ABSTRACT Undifferentiated pleomorphic sarcoma (UPS) has a favorable objective response rate to anti‐PD‐1 drugs compared with other sarcomas. Tertiary lymphoid structure (TLS) is a favorable prognostic factor and a biomarker for immune checkpoint inhibitors (ICIs). Nevertheless, there are limited data on the tumor microenvironment (TME) to support a good response to ICIs in sarcoma. Therefore, this study was conducted to investigate the impact of TLS on prognosis and TME. A total of 52 of UPS with wide resection were divided into intratumoral TLS, extratumoral TLS, and without TLS groups. Survival analysis and immunohistochemistry were performed to evaluate immune cells and immune checkpoint molecules, and multiplexed immunofluorescence was conducted to evaluate T‐cell exhaustion among the three groups. TLS was detected in 34 cases (65%), including 23 intratumoral TLS (44%) and 11 extratumoral TLS (21%) cases. Patients with TLS had significantly longer overall survival than those without TLS (log rank p = 0.020). The intratumoral TLS group had a significantly higher number of immune cells and higher expression of PD‐L1 and IDO‐1 than the without TLS group. Progenitor‐exhausted T cells were also observed in patients with UPS. In conclusion, these findings could help predict prognosis in patients with UPS. TLS was demonstrated to be a favorable prognostic factor in patients with UPS. Intratumoral TLS may be a biomarker for the response to ICIs, especially anti‐PD‐1 drugs.