• Kazue Yoneda, Taiji Kuwata, Masatoshi Kanayama, Masataka Mori, Toshinori Kawanami, Kazuhiro Yatera, Takayuki Ohguri, Masanori Hisaoka, Toshiyuki Nakayama, and Fumihiro Tanaka.
• Second Department of Surgery (Chest Surgery), University of Occupational and Environmental Health Japan, Kitakyushu, Japan.
• Br. J. Cancer. 2019 Sep 1; 121 (6): 490-496.

BackgroundConsolidation treatment with an anti-PD-L1 antibody, durvalumab, following concurrent chemo-radiotherapy (cCRT) has become a new standard of care for locally advanced non-small cell lung cancer (NSCLC). The rationale of PD-L1 blockade after cCRT is based on preclinical evidence suggesting that chemotherapy and radiotherapy up-regulate tumoural PD-L1 expression, which has not been shown in clinical studies.MethodsTo examine alteration in tumoural PD-L1 expression (tumour proportion score, TPS) and density of stromal CD8-positive tumour-infiltrating lymphocytes (CD8 + TILs) after cCRT, paired NSCLC samples obtained before and after cCRT were reviewed in comparison with those obtained before and after drug therapy.ResultsPD-L1 expression was significantly up-regulated after cCRT (median TPS, 1.0 at baseline versus 48.0 after cCRT; P < 0.001), but not after drug therapy. There was no significant correlation between baseline TPS and post-cCRT TPS. CD8 + TIL density was significantly increased after cCRT (median, 10.6 versus 39.1; P < 0.001), and higher post-cCRT CD8 + TIL density was associated with a higher pathologic response and with a favourable survival (P = 0.019).ConclusionTumoural PD-L1 expression was up-regulated after cCRT, which provides pathologic rationale for PD-L1 blockade following cCRT to improve prognosis. Stromal CD8 + TIL density was also increased after cCRT, and higher post-cCRT CD8 + TIL density was a favourable prognostic indicator.

47 keywords...

hide…