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Erschienen in: Gastric Cancer 1/2019

01.01.2019 | Original Article

Discordancy and changes in the pattern of programmed death ligand 1 expression before and after platinum-based chemotherapy in metastatic gastric cancer

verfasst von: Ji Hyun Yang, Hyunho Kim, Sang Young Roh, Myung Ah Lee, Jae Myung Park, Han Hee Lee, Cho Hyun Park, Han Hong Lee, Eun Sun Jung, Sung Hak Lee, Young Joon Lee, Moon Hyung Choi, Okran Kim, In-Ho Kim

Erschienen in: Gastric Cancer | Ausgabe 1/2019

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Abstract

Background

Our goal was to evaluate changes in PD-L1 expression in primary tumours of metastatic gastric cancer before and after chemotherapy.

Methods

We evaluated the PD-L1 expression of 72 patients with primary gastric cancer, before and after palliative first-line platinum-based chemotherapy, between January 2015 and March 2017. The PD-L1 ratio was defined as pre-chemotherapy PD-L1 expression divided by the post-chemotherapy PD-L1 expression.

Results

In 30 patients with PD-L1 negative pre-chemotherapy, 12 (40%) were positive post-chemotherapy; among the 42 patients with PD-L1 positive pre-chemotherapy, 24 (57.1%) were negative post-chemotherapy. The degree of PD-L1 expression decreased from 58.3% before chemotherapy to 41.7% after chemotherapy (P = 0.046). Among patients with complete response/partial response (CR/PR), the degree of PD-L1 expression decreased (P = 0.002), as well as PD-L1 positivity with statistical significance (P = 0.013) after chemotherapy, but not among patients with stable disease/progressive disease (SD/PD). Higher disease control rates (CR/PR/SD) were observed in patients with an elevated PD-L1 ratio (P = 0.043). Patients with a high PD-L1 ratio (> 1) were found to be associated with a better progression-free survival (HR 0.34, 95% CI 0.17–0.67, P = 0.002).

Conclusions

PD-L1 expression can change during chemotherapy. Moreover, changes in patterns of PD-L1 expression might be associated with patient prognosis and response to chemotherapy.
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Literatur
1.
Zurück zum Zitat Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61:69–90.CrossRefPubMed Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61:69–90.CrossRefPubMed
3.
Zurück zum Zitat Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, et al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 2010;376:687 – 97.CrossRefPubMed Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, et al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 2010;376:687 – 97.CrossRefPubMed
4.
Zurück zum Zitat Wilke H, Muro K, Van Cutsem E, Oh SC, Bodoky G, Shimada Y, et al. Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (RAINBOW): a double-blind, randomised phase 3 trial. Lancet Oncol. 2014;15:1224–35.CrossRefPubMed Wilke H, Muro K, Van Cutsem E, Oh SC, Bodoky G, Shimada Y, et al. Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (RAINBOW): a double-blind, randomised phase 3 trial. Lancet Oncol. 2014;15:1224–35.CrossRefPubMed
6.
Zurück zum Zitat Buchbinder EI, Desai A. CTLA-4 and PD-1 pathways: similarities, differences, and implications of their inhibition. Am J Clin Oncol. 2016;39:98–106.CrossRefPubMedPubMedCentral Buchbinder EI, Desai A. CTLA-4 and PD-1 pathways: similarities, differences, and implications of their inhibition. Am J Clin Oncol. 2016;39:98–106.CrossRefPubMedPubMedCentral
7.
Zurück zum Zitat Zou W, Chen L. Inhibitory B7-family molecules in the tumour microenvironment. Nat Rev Immunol. 2008;8:467–77.CrossRefPubMed Zou W, Chen L. Inhibitory B7-family molecules in the tumour microenvironment. Nat Rev Immunol. 2008;8:467–77.CrossRefPubMed
8.
Zurück zum Zitat Alsaab HO, Sau S, Alzhrani R, Tatiparti K, Bhise K, Kashaw SK, et al. PD-1 and PD-L1 checkpoint signaling inhibition for cancer immunotherapy: mechanism, combinations, and clinical outcome. Front Pharmacol. 2017;8:561.CrossRefPubMedPubMedCentral Alsaab HO, Sau S, Alzhrani R, Tatiparti K, Bhise K, Kashaw SK, et al. PD-1 and PD-L1 checkpoint signaling inhibition for cancer immunotherapy: mechanism, combinations, and clinical outcome. Front Pharmacol. 2017;8:561.CrossRefPubMedPubMedCentral
9.
Zurück zum Zitat Lote H, Cafferkey C, Chau I. PD-1 and PD-L1 blockade in gastrointestinal malignancies. Cancer Treat Rev. 2015;41:893–903.CrossRefPubMed Lote H, Cafferkey C, Chau I. PD-1 and PD-L1 blockade in gastrointestinal malignancies. Cancer Treat Rev. 2015;41:893–903.CrossRefPubMed
10.
Zurück zum Zitat Wainberg ZA, Jalal S, Muro K, Yoon HH, Garrido M, Golan T, et al. LBA28_PRKEYNOTE-059 Update: Efficacy and safety of pembrolizumab alone or in combination with chemotherapy in patients with advanced gastric or gastroesophageal (G/GEJ) cancer. Ann Oncol. 2017;28:mdx440.020–mdx440.020.CrossRef Wainberg ZA, Jalal S, Muro K, Yoon HH, Garrido M, Golan T, et al. LBA28_PRKEYNOTE-059 Update: Efficacy and safety of pembrolizumab alone or in combination with chemotherapy in patients with advanced gastric or gastroesophageal (G/GEJ) cancer. Ann Oncol. 2017;28:mdx440.020–mdx440.020.CrossRef
11.
Zurück zum Zitat Sacher AG, Gandhi L. Biomarkers for the clinical use of PD-1/PD-L1 inhibitors in non-small-cell lung cancer: a review. JAMA Oncol. 2016;2:1217–22.CrossRefPubMed Sacher AG, Gandhi L. Biomarkers for the clinical use of PD-1/PD-L1 inhibitors in non-small-cell lung cancer: a review. JAMA Oncol. 2016;2:1217–22.CrossRefPubMed
12.
Zurück zum Zitat Yuasa T, Masuda H, Yamamoto S, Numao N, Yonese J. Biomarkers to predict prognosis and response to checkpoint inhibitors. Int J Clin Oncol. 2017;22:629 – 34.CrossRefPubMedPubMedCentral Yuasa T, Masuda H, Yamamoto S, Numao N, Yonese J. Biomarkers to predict prognosis and response to checkpoint inhibitors. Int J Clin Oncol. 2017;22:629 – 34.CrossRefPubMedPubMedCentral
14.
Zurück zum Zitat Lim SH, Hong M, Ahn S, Choi YL, Kim KM, Oh D, et al. Changes in tumour expression of programmed death-ligand 1 after neoadjuvant concurrent chemoradiotherapy in patients with squamous oesophageal cancer. Eur J Cancer. 2016;52:1–9.CrossRefPubMed Lim SH, Hong M, Ahn S, Choi YL, Kim KM, Oh D, et al. Changes in tumour expression of programmed death-ligand 1 after neoadjuvant concurrent chemoradiotherapy in patients with squamous oesophageal cancer. Eur J Cancer. 2016;52:1–9.CrossRefPubMed
15.
Zurück zum Zitat Luo M, Fu L. The effect of chemotherapy on programmed cell death 1/programmed cell death 1 ligand axis: some chemotherapeutical drugs may finally work through immune response. Oncotarget. 2016;7:29794–803.PubMedPubMedCentral Luo M, Fu L. The effect of chemotherapy on programmed cell death 1/programmed cell death 1 ligand axis: some chemotherapeutical drugs may finally work through immune response. Oncotarget. 2016;7:29794–803.PubMedPubMedCentral
16.
Zurück zum Zitat Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45:228–47.CrossRefPubMed Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45:228–47.CrossRefPubMed
17.
Zurück zum Zitat Boger C, Behrens HM, Mathiak M, Kruger S, Kalthoff H, Rocken C. PD-L1 is an independent prognostic predictor in gastric cancer of Western patients. Oncotarget. 2016;7:24269–83.CrossRefPubMedPubMedCentral Boger C, Behrens HM, Mathiak M, Kruger S, Kalthoff H, Rocken C. PD-L1 is an independent prognostic predictor in gastric cancer of Western patients. Oncotarget. 2016;7:24269–83.CrossRefPubMedPubMedCentral
18.
Zurück zum Zitat Meng X, Huang Z, Teng F, Xing L, Yu J. Predictive biomarkers in PD-1/PD-L1 checkpoint blockade immunotherapy. Cancer Treat Rev. 2015;41:868–76.CrossRefPubMed Meng X, Huang Z, Teng F, Xing L, Yu J. Predictive biomarkers in PD-1/PD-L1 checkpoint blockade immunotherapy. Cancer Treat Rev. 2015;41:868–76.CrossRefPubMed
19.
Zurück zum Zitat Garon EB, Rizvi NA, Hui R, Leighl N, Balmanoukian AS, Eder JP, et al. Pembrolizumab for the treatment of non-small-cell lung cancer. N Engl J Med. 2015;372:2018–28.CrossRefPubMed Garon EB, Rizvi NA, Hui R, Leighl N, Balmanoukian AS, Eder JP, et al. Pembrolizumab for the treatment of non-small-cell lung cancer. N Engl J Med. 2015;372:2018–28.CrossRefPubMed
20.
Zurück zum Zitat Balar AV, Galsky MD, Rosenberg JE, Powles T, Petrylak DP, Bellmunt J, et al. Atezolizumab as first-line treatment in cisplatin-ineligible patients with locally advanced and metastatic urothelial carcinoma: a single-arm, multicentre, phase 2 trial. Lancet. 2017;389:67–76.CrossRefPubMed Balar AV, Galsky MD, Rosenberg JE, Powles T, Petrylak DP, Bellmunt J, et al. Atezolizumab as first-line treatment in cisplatin-ineligible patients with locally advanced and metastatic urothelial carcinoma: a single-arm, multicentre, phase 2 trial. Lancet. 2017;389:67–76.CrossRefPubMed
21.
Zurück zum Zitat Schatton T, Schutte U, Frank NY, Zhan Q, Hoerning A, Robles SC, et al. Modulation of T-cell activation by malignant melanoma initiating cells. Cancer Res. 2010;70:697–708.CrossRefPubMedPubMedCentral Schatton T, Schutte U, Frank NY, Zhan Q, Hoerning A, Robles SC, et al. Modulation of T-cell activation by malignant melanoma initiating cells. Cancer Res. 2010;70:697–708.CrossRefPubMedPubMedCentral
22.
Zurück zum Zitat Shen JK, Cote GM, Choy E, Yang P, Harmon D, Schwab J, et al. Programmed cell death ligand 1 expression in osteosarcoma. Cancer Immunol Res. 2014;2:690–8.CrossRefPubMedPubMedCentral Shen JK, Cote GM, Choy E, Yang P, Harmon D, Schwab J, et al. Programmed cell death ligand 1 expression in osteosarcoma. Cancer Immunol Res. 2014;2:690–8.CrossRefPubMedPubMedCentral
23.
Zurück zum Zitat Fujita Y, Yagishita S, Hagiwara K, Yoshioka Y, Kosaka N, Takeshita F, et al. The clinical relevance of the miR-197/CKS1B/STAT3-mediated PD-L1 network in chemoresistant non-small-cell lung cancer. Mol Ther. 2015;23:717–27.CrossRefPubMedPubMedCentral Fujita Y, Yagishita S, Hagiwara K, Yoshioka Y, Kosaka N, Takeshita F, et al. The clinical relevance of the miR-197/CKS1B/STAT3-mediated PD-L1 network in chemoresistant non-small-cell lung cancer. Mol Ther. 2015;23:717–27.CrossRefPubMedPubMedCentral
24.
Zurück zum Zitat Sheng J, Fang W, Yu J, Chen N, Zhan J, Ma Y, et al. Expression of programmed death ligand-1 on tumor cells varies pre and post chemotherapy in non-small cell lung cancer. Sci Rep. 2016;6:20090.CrossRefPubMedPubMedCentral Sheng J, Fang W, Yu J, Chen N, Zhan J, Ma Y, et al. Expression of programmed death ligand-1 on tumor cells varies pre and post chemotherapy in non-small cell lung cancer. Sci Rep. 2016;6:20090.CrossRefPubMedPubMedCentral
25.
Zurück zum Zitat Zhang P, Su DM, Liang M, Fu J. Chemopreventive agents induce programmed death-1-ligand 1 (PD-L1) surface expression in breast cancer cells and promote PD-L1-mediated T cell apoptosis. Mol Immunol. 2008;45:1470–6.CrossRefPubMed Zhang P, Su DM, Liang M, Fu J. Chemopreventive agents induce programmed death-1-ligand 1 (PD-L1) surface expression in breast cancer cells and promote PD-L1-mediated T cell apoptosis. Mol Immunol. 2008;45:1470–6.CrossRefPubMed
26.
Zurück zum Zitat Ghebeh H, Lehe C, Barhoush E, Al-Romaih K, Tulbah A, Al-Alwan M, et al. Doxorubicin downregulates cell surface B7-H1 expression and upregulates its nuclear expression in breast cancer cells: role of B7-H1 as an anti-apoptotic molecule. Breast Cancer Res. 2010;12:R48.CrossRefPubMedPubMedCentral Ghebeh H, Lehe C, Barhoush E, Al-Romaih K, Tulbah A, Al-Alwan M, et al. Doxorubicin downregulates cell surface B7-H1 expression and upregulates its nuclear expression in breast cancer cells: role of B7-H1 as an anti-apoptotic molecule. Breast Cancer Res. 2010;12:R48.CrossRefPubMedPubMedCentral
27.
Zurück zum Zitat Kim JW, Nam KH, Ahn SH, Park do J, Kim HH, Kim SH, et al. Prognostic implications of immunosuppressive protein expression in tumors as well as immune cell infiltration within the tumor microenvironment in gastric cancer. Gastric Cancer. 2016;19:42–52.CrossRefPubMed Kim JW, Nam KH, Ahn SH, Park do J, Kim HH, Kim SH, et al. Prognostic implications of immunosuppressive protein expression in tumors as well as immune cell infiltration within the tumor microenvironment in gastric cancer. Gastric Cancer. 2016;19:42–52.CrossRefPubMed
28.
Zurück zum Zitat Wu C, Zhu Y, Jiang J, Zhao J, Zhang XG, Xu N. Immunohistochemical localization of programmed death-1 ligand-1 (PD-L1) in gastric carcinoma and its clinical significance. Acta Histochem. 2006;108:19–24.CrossRefPubMed Wu C, Zhu Y, Jiang J, Zhao J, Zhang XG, Xu N. Immunohistochemical localization of programmed death-1 ligand-1 (PD-L1) in gastric carcinoma and its clinical significance. Acta Histochem. 2006;108:19–24.CrossRefPubMed
29.
Zurück zum Zitat Thompson RH, Kuntz SM, Leibovich BC, Dong H, Lohse CM, Webster WS, et al. Tumor B7-H1 is associated with poor prognosis in renal cell carcinoma patients with long-term follow-up. Cancer Res. 2006;66:3381–5.CrossRefPubMed Thompson RH, Kuntz SM, Leibovich BC, Dong H, Lohse CM, Webster WS, et al. Tumor B7-H1 is associated with poor prognosis in renal cell carcinoma patients with long-term follow-up. Cancer Res. 2006;66:3381–5.CrossRefPubMed
30.
Zurück zum Zitat Zang X, Thompson RH, Al-Ahmadie HA, Serio AM, Reuter VE, Eastham JA, et al. B7-H3 and B7x are highly expressed in human prostate cancer and associated with disease spread and poor outcome. Proc Natl Acad Sci USA. 2007;104:19458–63.CrossRefPubMedPubMedCentral Zang X, Thompson RH, Al-Ahmadie HA, Serio AM, Reuter VE, Eastham JA, et al. B7-H3 and B7x are highly expressed in human prostate cancer and associated with disease spread and poor outcome. Proc Natl Acad Sci USA. 2007;104:19458–63.CrossRefPubMedPubMedCentral
31.
Zurück zum Zitat Thompson ED, Zahurak M, Murphy A, Cornish T, Cuka N, Abdelfatah E, et al. Patterns of PD-L1 expression and CD8 T cell infiltration in gastric adenocarcinomas and associated immune stroma. Gut. 2017;66:794–801.CrossRefPubMed Thompson ED, Zahurak M, Murphy A, Cornish T, Cuka N, Abdelfatah E, et al. Patterns of PD-L1 expression and CD8 T cell infiltration in gastric adenocarcinomas and associated immune stroma. Gut. 2017;66:794–801.CrossRefPubMed
32.
Zurück zum Zitat Jiang W, Liu K, Guo Q, Cheng J, Shen L, Cao Y, et al. Tumor-infiltrating immune cells and prognosis in gastric cancer: a systematic review and meta-analysis. Oncotarget. 2017;8:62312–29.PubMedPubMedCentral Jiang W, Liu K, Guo Q, Cheng J, Shen L, Cao Y, et al. Tumor-infiltrating immune cells and prognosis in gastric cancer: a systematic review and meta-analysis. Oncotarget. 2017;8:62312–29.PubMedPubMedCentral
33.
Metadaten
Titel
Discordancy and changes in the pattern of programmed death ligand 1 expression before and after platinum-based chemotherapy in metastatic gastric cancer
verfasst von
Ji Hyun Yang
Hyunho Kim
Sang Young Roh
Myung Ah Lee
Jae Myung Park
Han Hee Lee
Cho Hyun Park
Han Hong Lee
Eun Sun Jung
Sung Hak Lee
Young Joon Lee
Moon Hyung Choi
Okran Kim
In-Ho Kim
Publikationsdatum
01.01.2019
Verlag
Springer Japan
Erschienen in
Gastric Cancer / Ausgabe 1/2019
Print ISSN: 1436-3291
Elektronische ISSN: 1436-3305
DOI
https://doi.org/10.1007/s10120-018-0842-x

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