Landscape of Immune Checkpoint Inhibition in Carcinosarcoma (MMMT): Analysis of IDO-1, PD-L1 and PD-1.

BACKGROUND: Carcinosarcoma (CS) or malignant mixed Müllerian tumor (MMMT), is a rare malignant biphasic tumor, which contains both a malignant epithelial and mesenchymal component. That being said, they have an aggressive clinical course. Given that immune checkpoint inhibitors have mustered significant excitement in the oncology world - immunotherapy could offer significant promise to this poor prognostic cancer subtype. A total of 75 carcinosarcoma cases were identified in our institutional database from 2010 to 2019 and immunohistochemistry for PD-L1, PD-1 and IDO-1 was performed. Out of the 75 patients, 65(87 %) demonstrated >1 % PD-1 expression and 50(67 %) expressed >1 % PD-L1 in either the tumoral and immune stromal components. 29 (39 %) cases demonstrated >20 % PD-1 expression and 14 (19 %) cases expressed >20 % PD-L1. 41(55 %) cases demonstrating co-expression of PD-1 and PD-L1. For IDO-1 64 (85 %) patients showed at least >5 %, while 34 (45 %) showed staining above 20 %. 45 patients (60 %) showed co-expression of IDO-1 and PD-L1, while 59 (79 %) patients had co-expression of IDO and PD-1 above 5 and 1 % respectively. Regarding clinicopathologcial features; older patients (> 65) were more likely to express PD-L1 (>1 %) and IDO-1 (>20 %). For tumor size, IDO-1 expression (>5 %), along with PD-1/IDO-1 Co-expression (>1/5 %), was associated with larger tumor size (>5cm). For myometrial invasion, CSs with >50 % invasion were more likely to express IDO-1 (>20 %) and PD-1/IDO-1 (>1/5 %). Ultimately, the effect of IDO-1, PD-1 and PD-L1 on the clinical profile may be less important than its potential use as a immunotherapeutic, where safe and effective corresponding drugs could be used to treat particular patient populations. Future clinical trials are needed to decipher the association between immune check point inhibitor expression and therapeutic response. This is the only way to definitively prove immune checkpoint immunohistochemistry as predictive biomarkers in this cancer subtype.