Major histocompatibility complex II serves as a prognostic biomarker in resectable pulmonary sarcomatoid carcinoma: development of a prediction model.

BACKGROUND

Pulmonary sarcomatoid carcinoma (PSC) is a rare pulmonary malignancy, exhibiting a poor outcome even after complete resection. Major histocompatibility complex II (MHC-II) is a critical molecule in priming anti-tumor immunity, while its expression and the prognostic role in PSC have been rarely investigated. This study aimed to evaluate intratumoral MHC-II expression and assess its prognostic value in resected PSC for the development of MHC-II-based prediction models.

METHODS

In this retrospective study, we enrolled 86 patients with resected PSC. Immunohistochemistry (IHC) was used to evaluate MHC-II expression. Patients were randomly divided into training and validation cohorts. Least absolute shrinkage and selection operator (LASSO) regression was used to select predictors and construct prognostic models for progression-free survival (PFS) and overall survival (OS). Model performance was assessed using the area under the curve (AUC). Additionally, public RNA sequencing data (n=17) from Gene Expression Omnibus (GEO) were used for bioinformatics analysis.

RESULTS

We demonstrated positive MHC-II expression on both tumor cells (22.09%) and tumor-infiltrating lymphocytes (TILs) (36.05%). Higher expression of MHC-II on both tumor cells and TILs indicated longer PFS (P=0.005 and P=0.042) and OS. The MHC-II-based prognostic models showed performance in the validation cohort with AUC exceeding 0.70 for both PFS and OS. Bioinformatics analysis suggested that samples with high MHC-II expression had higher infiltration levels of CD4+ T cells, CD8+ T cells, dendritic cells (DCs), and M1 macrophages. Meanwhile, programmed cell death protein 1 (PD-1) signaling was also upregulated in MHC-IIhigh group.

CONCLUSIONS

Our study uncovered the expression of MHC-II and its prognostic role in PSC. High expression of MHC-II might induce an inflamed tumor microenvironment (TME). And anti-PD-1 treatment might be a promising treatment for MHC-IIhigh PSC.