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

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

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