1935P - Exploration of tertiary lymphatic structure in soft tissue sarcoma for the prognostic and immunotherapy response

Background

The tertiary lymphoid structure (TLS) is an important part of the tumor microenvironment. It generates circulating immune cells and inhibits tumor growth and progression, which is closely related to the efficacy of immunotherapy.

Methods

This study collected the transcriptome information and clinical data of 10327 tumor samples and 730 normal samples of 33 cancer types from the TCGA database. Based on previous literature, three sets of TLS-related gene sets were selected and merged into the total TLS gene set. The TLS enrichment scores were calculated by the GSVA algorithm. Further, utilize TIMER 2.0 and CIBERSORTNE algorithms to analyze the distribution of tumor-infiltrating immune cells. Based on the enrichment score of TLS, sarcoma patients were divided into three TLS subtypes via the "hclust" R package. TLS-related prognostic core genes were screened via Lasso Cox and multivariate Cox regression and further used to establish the TLS-related prognostic signature. The public immunotherapy cohorts and our center immunotherapy patients were used to validate the efficacy of immunotherapy.

Results

The TLS gene set enrichment score established in this study is significantly positively correlated with immune cell infiltration such as T cells, B cells, and DC cells, which can reflect the TLS status in tumor tissue. Kaplan Meier survival analysis showed that patients with high TLS had better overall survival and progression-free survival compared to patients with low TLS. Through Lasso Cox and multivariate Cox regression, two TLS-related prognostic core genes (TNFRSF14 and DUSP9) were ultimately screened, and a TLS-related prognostic signature was established. Immunohistochemistry showed that the expression of TNFRSF14 was increased and the expression of DUSP9 was reduced in patients with soft tissue sarcoma who achieved optimal immunotherapy.

Conclusions

The TLS-Total gene set, TLS-related prognostic signature, TNFRSF14, and DUSP9 selected in this study can predict the prognosis of patients with soft tissue sarcoma. TNFRSF14 and DUSP9 are associated with immune cell infiltration, which can indicate the efficacy of immunotherapy and may become new predictive markers of immunotherapy efficacy.

Clinical trial identification

No

Editorial acknowledgement

No

Legal entity responsible for the study

The authors.

Funding

Natural Science Basic Research Program of Shaanxi (No. 2021JZ-35).

Disclosure

All authors have declared no conflicts of interest.