Sequential tracking of PD-L1 expression and RAD50 induction in circulating tumor and stromal cells of lung cancer patients undergoing radiotherapy

Purpose: Evidence suggests that PD-L1 can be induced with Results: Only 24% of primary biopsies had sufficient tissue for radiotherapy and may be an immune escape mechanism in PD-L1 testing, tested with IHC clones 22c3 and 28-8. A CTC or cancer. Monitoring this response is limited, as repetitive biop-CAML was detectable in 93% and 100% of samples, prior to and sies during therapy are impractical, dangerous, and miss tumor after radiotherapy, respectively. RAD50 foci significantly stromal cells. Monitoring PD-L1 expression in both circulating increased in CTCs (>7, P < 0.001) and CAMLs (>10, P ¼ tumor cells (CTCs) and circulating stromal cells (CStCs) in 0.001) after radiotherapy, confirming their origin from the radi-blood-based biopsies might be a practical alternative for ated site. PD-L1 expression increased overall, 1.6 in CTCs (P ¼ sequential, noninvasive assessment of changes in tumor and 0.021) and 1.8 in CAMLs (P ¼ 0.004): however, individual stromal cells. patient PD-L1 expression varied, consistently low/negative Experimental Design: Peripheral blood was collected (51%), consistently high (17%), or induced (31%). before and after radiotherapy from 41 patients with lung Conclusions: These data suggest that RAD50 foci formation in cancer, as were primary biopsies. We evaluated the expres-CTCs and CAMLs may be used to track cells subjected to radiation sion of PD-L1 and formation of RAD50 foci in CTCs and a occurring at primary tumors, and following PD-L1 expression in CStC subtype, cancer-associated macrophage-like cells circulating cells may be used as a surrogate for tracking adaptive (CAMLs), in response to DNA damage caused by radiother-changes in immunotherapeutic targets.