바로가기  >

Abstract

Purpose: 

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 are impractical, dangerous, and miss 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, noninvasive assessment of changes in tumor and stromal cells.

Experimental Design:

Peripheral blood was collected before and after radiotherapy from 41 patients with lung cancer, as were 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.

Results:

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 (>7×, P < 0.001) and CAMLs (>10×, P = 0.001) after radiotherapy, confirming their origin from the radiated site. PD-L1 expression increased overall, 1.6× in CTCs (P = 0.021) and 1.8× in CAMLs (P = 0.004): however, individual patient PD-L1 expression varied, consistently low/negative (51%), consistently high (17%), or induced (31%).

Conclusions:

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.

Author information

Adams DL1, Adams DK2, He J3, Kalhor N3, Zhang M4, Xu T3, Gao H3, Reuben JM3, Qiao Y3, Komaki R3, Liao Z3, Edelman MJ5, Tang CM6, Lin SH7.

1 Creatv MicroTech, Inc., Monmouth Junction, New Jersey. dan@creatvmicrotech.com shlin@mdanderson.org.

2 Rutgers, the State University of New Jersey, New Brunswick, New Jersey.

3 MD Anderson Cancer Center, Houston, Texas.

4 Hebei General Hospital, Shijiazhuang, China.

5 Fox Chase Cancer Center, Philadelphia, Pennsylvania.

6 Creatv MicroTech, Inc., Potomac, Maryland.

7 MD Anderson Cancer Center, Houston, Texas. dan@creatvmicrotech.com shlin@mdanderson.org.