Circulating tumor cells and clusters exhibiting expression of PD-L1 in colorectal patients.

Abstract

e15038 Background: The role of circulating tumor cells (CTCs) has been well established in the prediction of survival in metastatic settings, namely breast, colorectal, and prostate. While its utility has been limited due to the exorbitant cost, sensitivity, accuracy, and by using cut-off numbers. The significant role of CTCs from extravasation to invasion, for tumor microenvironment, and tumor burden is more implicative over to its current limited clinical utility. Especially, its role in monitoring the patients for minimal cellular residual disease (MCRD) in early-stage cancer remains unexplored, especially post-surgery, therapy duration decisions in cancers like colorectal, and finally longitudinal patient monitoring for recurrence. Accounting dynamic PD-L1 expression on CTCs may reveal incomplete tumor resection/ treatment and cell dormancy in circulation overcoming the immune elimination. We report the expression of PD-L1 on CTCs and clusters in colorectal cancers. Methods: Retrospectively, we analyzed 666 (63.06% Male and 36.94 Female) early-stage to late-stage colorectal cancer patients for the presence of CTCs with and without the expression of PD-L1 and CTC clusters. CTCs were positively detected using the OncoDiscover platform approved by CDSCO- India in 1.5 ml peripheral blood. CTCs were identified as positive if they were EpCAM+ve, CK18+ve, DAPI+ve, and CD45-ve and acquired using an automated Zeiss Microscope. Results: At baseline sample analysis, 74.25% (n = 591) of the patients showed ≥1CTCs per 1.5 ml of blood. The CTC distribution in this study ranged from 1-20 CTCs. Whereas, 74.62% (n = 441) of patients with CTCs showed the expression of PD-L1. Notably, the highest number of CTCs was observed at ~ 25.86% (n = 352) in the age group 61-70. 13.00% (n = 156) of patients showed the presence of CTC clusters. Interestingly, over to baseline most of the CTC clusters were observed post follow-up The mean CTC (including clusters) and CTCs with PD-L1 was 1.71 and 1.02, respectively. Conclusions: PD-L1 expression on CTCs may reveal their ability to be dormant in circulation for longer due to protein overexpression on the cell surface overcoming the elimination from immune T cells. CTC-PD-L1 assay has great potential as as utility in patient surveillance before and post-treatment for accounting MCRD. More clinical studies in this direction are highly desired.