Association of circulating tumor cells with PD-L1 expression and clusters in confirmative tumor thrombus in selective solid cancers.

Abstract

e16191 Background: Tumor thrombus (TT) is often an incidental, leading direct extension of tumor cells into a blood vein. It is commonly observed in renal cell carcinoma (RCC), hepatocellular carcinoma (HCC), and Wilms tumor. TT significantly worsens the prognosis and alters staging. Further the evidence of TT is often observed at locations like renal vein, inferior vena cava, and portal vein. Thus it requires multidisciplinary evaluation due to its aggressive nature and potential for obstruction or embolization. To differentiate tumor thrombus, diagnostic approaches revolve aroundimaging, such as CT or MRI, from a "bland" thrombus (a blood clot).We evaluated if there is any association and role of circulating tumor cells (CTCs) expressing immune-relevant markers e.g. PD-L in TT. Thus presence of CTCs originating from TT margins may refine risk stratification and therapeutic decision-making. Methods: In an observational study, total of 12 patients with HCC (n = 4), pancreatic (n = 3), liver (n = 3), RCC (n = 1), gallbladder (GB) (n = 1), etc. with confirmative with TT (age 51-80) underwent blood analysis for presence of CTCs with PD-L1 expression at baseline (B) and 3 patients with a follow up (FU). Samples were processed using OncoDiscover CTC enrichments CDSCO approved technology on an automated Zeiss microscope by confirmative EpCAM⁺, CK18⁺, DAPI⁺, CD45⁻ and PD-L1⁺. Results: Total of 16 CTCs were detected in 10 patient’s (83.33%) 1.5 ml of blood samples ranging 1-6 CTCs. At baseline, HCC, pancreatic, RCC, GB, and other cancers showed presence of CTCs with PD-L1 expression. In FU samples revealed the persistent CTC positivity, although PD-L1 positive CTCs were reduced. The mean CTC distribution was observed to be 1.33 with CK 18 expression, while expression of PD-L1 + ve CTCs were observed in a substantial subset, with mean distribution 0.67 (9 CTCs /12 patients). These cells are indicative with immune-evasive potential. CTC clusters were rare and detected in only 1 HCC patient, but persisted even at FU. Both male and female patients demonstrated comparable CTC positivity. Conclusions: The presence of CTCs in peripheral blood highlights active dissemination in TT margins. Although CTC clusters were infrequent, their occurrence may indicate heightened metastatic risk. For the first time we showed presence of CTCs and shedding from thrombus margins into blood circulation. More studies in this direction are suggested. Clinical trial information: IESC/FP /24/2023 (Acronym: USGCTC).