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Clinical Trial
. 2019 Sep;121(6):490-496.
doi: 10.1038/s41416-019-0541-3. Epub 2019 Aug 7.

Alteration in tumoural PD-L1 expression and stromal CD8-positive tumour-infiltrating lymphocytes after concurrent chemo-radiotherapy for non-small cell lung cancer

Kazue Yoneda  1 , Taiji Kuwata  1 , Masatoshi Kanayama  1 , Masataka Mori  1 , Toshinori Kawanami  2 , Kazuhiro Yatera  2 , Takayuki Ohguri  3 , Masanori Hisaoka  4 , Toshiyuki Nakayama  5 , Fumihiro Tanaka  6
Affiliations
Clinical Trial

Alteration in tumoural PD-L1 expression and stromal CD8-positive tumour-infiltrating lymphocytes after concurrent chemo-radiotherapy for non-small cell lung cancer

Kazue Yoneda et al. Br J Cancer. 2019 Sep.

Abstract

Background: Consolidation 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.

Methods: To 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.

Results: PD-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).

Conclusion: Tumoural 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.

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Conflict of interest statement

K.Y. reports grants from ASAHI KASEI PHARMA CORPORATION, grants and personal fees from Astellas Pharma Inc., grants and personal fees from AstraZeneca K.K., grants and personal fees from Bristol-Myers Squibb K.K., grants and personal fees from CHUGAI PHARMACEUTICAL CO., LTD., grants from DAIICHI SANKYO COMPANY, LIMITED, grants from Daiwa Securities Health Foundation, grants and personal fees from Eli Lilly Japan K.K., grants from FUJIFILM Pharma Co., Ltd., grants from Fukuda Denshi Co., Ltd., grants and personal fees from GlaxoSmithKline K.K., grants from KAKENHI (Grants-in-Aid for Scientific Research) (C), grants from KYORIN Pharmaceutical Co.,Ltd., grants from Kyowa Hakko Kirin Co., Ltd., grants from Meiji Seika, grants and personal fees from MSD K.K. a subsidiary of Merck & Co.,Inc., grants from Mylan Inc., grants from Nippon Boehringer lngelheim Co., Ltd., grants from North East, grants and personal fees from Novartis Pharma K.K., grants from ONO PHARMACEUTICAL CO., LTD., grants from Oxford Immunotec, Inc., grants and personal fees from Pfizer Inc., grants and personal fees from Shionogi & Co., Ltd., grants from Sumitomo Dainippon Pharma Co., Ltd., grants and personal fees from TAIHO Pharmaceutical Co., Ltd., grants and personal fees from Taisho Toyama Pharmaceutical Co., Ltd., grants and personal fees from TEIJIN HOME HEALTHCARE LIMITED., outside the submitted work. F.T. reports grants and personal fees from ASAHI KASEI PHARMA CO, grants from Astellas Pharma Inc., grants and personal fees from AstraZeneca K.K., personal fees from Bristol-Myers Squibb K.K., grants and personal fees from CHUGAI PHARMACEUTICAL CO., LTD., grants and personal fees from Eli Lilly Japan K.K., grants and personal fees from Kyowa Hakko Kirin Co., Ltd., grants and personal fees from MSD K.K., grants and personal fees from Novartis Pharma K.K., grants and personal fees from ONO PHARMACEUTICAL CO., LTD., personal fees from Pfizer Inc., grants and personal fees from Shionogi & Co., Ltd., grants and personal fees from TAIHO Pharmaceutical Co., Ltd., grants from Eizai Co. Ltd., grants and personal fees from Nippon Boehringer Ingelheim Co. Ltd., personal fees from Johnson & Johnson Co. Ltd., personal fees from Covidien Japan Co. Ltd., outside the submitted work. The remaining authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Alteration in PD-L1 expression on tumour cells after drug therapy or concurrent chemo-radiotherapy. PD-L1 programmed death ligand-1, TPS tumour proportion score, CT chemotherapy, cCRT concurrent chemo-radiotherapy
Fig. 2
Fig. 2
Alteration in density of CD8-positive tumour-infiltrating lymphocytes after drug therapy or concurrent chemo-radiotherapy. CD8 + TIL CD8-positive tumour-infiltrating lymphocyte, CT chemotherapy, cCRT concurrent chemo-radiotherapy
Fig. 3
Fig. 3
Receiver operating characteristics curve for programmed death ligand-1 (PD-L1) expression on tumour cells or density of stromal CD8-positive tumour-infiltrating lymphocytes to predict death or recurrence after surgery following concurrent chemo-radiotherapy. PD-L1 programmed death ligand-1, TPS tumour proportion score, cCRT concurrent chemo-radiotherapy, CD8 + TIL CD8-positive tumour-infiltrating lymphocyte, AUC area under curve
Fig. 4
Fig. 4
Recurrence-free survival curve after surgery following concurrent chemo-radiotherapy according to programmed death ligand-1 (PD-L1) expression on tumour cells or density of CD8-positive tumour-infiltrating lymphocytes. PD-L1 programmed death ligand-1, TPS tumour proportion score, cCRT concurrent chemo-radiotherapy, CD8 + TIL CD8-positive tumour-infiltrating lymphocyte
Fig. 5
Fig. 5
Overall survival curve after surgery following concurrent chemo-radiotherapy according to programmed death ligand-1 (PD-L1) expression on tumour cells or density of stromal CD8-positive tumour-infiltrating lymphocytes. PD-L1 programmed death ligand-1, TPS tumour proportion score, cCRT concurrent chemo-radiotherapy, CD8 + TIL CD8-positive tumour-infiltrating lymphocyte
See this image and copyright information in PMC

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