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Journal of Cancer Research and Clinical Oncology

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14.03.2019 | Original Article – Clinical Oncology

Prognostic relevance of programmed cell death-ligand 1 expression and CD8+ TILs in rectal cancer patients before and after neoadjuvant chemoradiotherapy

verfasst von: Tsung-Wei Chen, Kevin Chih-Yang Huang, Shu-Fen Chiang, William Tzu-Liang Chen, Tao-Wei Ke, K. S. Clifford Chao

Erschienen in: Journal of Cancer Research and Clinical Oncology | Ausgabe 4/2019

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Abstract

Purpose/background

Radiotherapy has been recently reported to boost the therapeutic response of immune checkpoint blockade (ICB); however, few studies have focused on programmed cell death-ligand 1 (PD-L1) expression in locally advanced rectal cancer (LARC) patients who receive preoperative neoadjuvant chemoradiotherapy (neoCRT). The aim of the present study was to investigate the PD-L1 expression status and CD8+ intra-tumoral infiltrating lymphocytes (TILs) before and after neoCRT and its association with clinicopathological characteristics in rectal cancer.

Materials and methods

Immunostainings of PD-L1 and CD8+ TILs were performed in 112 pair-matched LARC patients treated by neoCRT. Tumor PD-L1 expression and CD8+ TILs within the tumor microenvironment before and after neoCRT were evaluated via immunohistochemistry.

Results

High tumor PD-L1 expression was significantly increased from 50 to 63%, and high CD8+ TILs counts were also slightly increased from 32 to 35% after neoCRT treatment. High tumor PD-L1 before and after neoCRT was associated with improved disease-free survival (DFS, pre-neoCRT: p = 0.003 and post-neoCRT: p = 0.003) and overall survival (OS, pre-neoCRT: p = 0.045 and post-neoCRT: p = 0.0001). High CD8+ TILs before neoCRT was associated with improved DFS (p = 0.057), and it was significantly associated with improved DFS after neoCRT (p = 0.039). Patients with high tumor PD-L1 and CD8+ TILs before and after neoCRT were significantly associated with improved DFS (pre-neoCRT: p = 0.004 and post-neoCRT: p = 0.006).

Conclusion

The present results provide evidence that tumor PD-L1 expression and recruitment of CD8+ TILs within the tumor microenvironment were increased by neoCRT treatment. Tumor PD-L1 and CD8+ TILs are prognostic biomarkers for the survival of LARC patients treated with neoCRT.

Balko JM, Black EP (2009) A gene expression predictor of response to EGFR-targeted therapy stratifies progression-free survival to cetuximab in KRAS wild-type metastatic colorectal cancer. BMC Cancer 9:145. https://doi.org/10.1186/1471-2407-9-145 CrossRefPubMedPubMedCentral

Baptista MZ, Sarian LO, Derchain SF, Pinto GA, Vassallo J (2016) Prognostic significance of PD-L1 and PD-L2 in breast cancer. Hum Pathol 47:78–84. https://doi.org/10.1016/j.humpath.2015.09.006 CrossRefPubMed

Chiang SF et al (2018) Upregulation of tumor PD-L1 by neoadjuvant chemoradiotherapy (neoCRT) confers improved survival in patients with lymph node metastasis of locally advanced rectal cancers. Cancer Immunol Immunother. https://doi.org/10.1007/s00262-018-2275-0 CrossRefPubMed

Conde-Muino R, Cuadros M, Zambudio N, Segura-Jimenez I, Cano C, Palma P (2015) Predictive biomarkers to chemoradiation in locally advanced rectal cancer. Biomed Res Int 2015:921435 https://doi.org/10.1155/2015/921435 CrossRefPubMedPubMedCentral

Droeser RA et al (2013) Clinical impact of programmed cell death ligand 1 expression in colorectal cancer. Eur J Cancer 49:2233–2242. https://doi.org/10.1016/j.ejca.2013.02.015 CrossRefPubMed

Dudley JC, Lin MT, Le DT, Eshleman JR (2016) Microsatellite Instability as a Biomarker for PD-1 Blockade. Clin Cancer Res 22:813–820. https://doi.org/10.1158/1078-0432.CCR-15-1678 CrossRefPubMed

Dworak O, Keilholz L, Hoffmann A (1997) Pathological features of rectal cancer after preoperative radiochemotherapy. Int J Colorectal Dis 12:19–23CrossRefPubMed

Gameiro SR, Jammeh ML, Wattenberg MM, Tsang KY, Ferrone S, Hodge JW (2014) Radiation-induced immunogenic modulation of tumor enhances antigen processing and calreticulin exposure, resulting in enhanced T-cell killing. Oncotarget 5:403–416. https://doi.org/10.18632/oncotarget.1719 CrossRefPubMed

Goode EL et al (2017) Dose-response association of CD8+ tumor-infiltrating lymphocytes and survival time in high-grade serous ovarian. Cancer JAMA Oncol 3:e173290. https://doi.org/10.1001/jamaoncol.2017.3290 CrossRefPubMed

Hecht M et al (2016) PD-L1 is upregulated by radiochemotherapy in rectal adenocarcinoma patients and associated with a favourable prognosis. Eur J Cancer 65:52–60. https://doi.org/10.1016/j.ejca.2016.06.015 CrossRefPubMed

Hirano F et al (2005) Blockade of B7-H1 and PD-1 by monoclonal antibodies potentiates cancer therapeutic immunity. Cancer Res 65:1089–1096PubMed

Huang CY et al (2018a) HMGB1 promotes ERK-mediated mitochondrial Drp1 phosphorylation for chemoresistance through RAGE in colorectal cancer. Cell Death Dis 9:1004. https://doi.org/10.1038/s41419-018-1019-6 CrossRefPubMedPubMedCentral

Huang CY et al (2018b) Cytosolic high-mobility group box protein 1 (HMGB1) and/or PD-1 + TILs in the tumor microenvironment may be contributing prognostic biomarkers for patients with locally advanced rectal cancer who have undergone neoadjuvant chemoradiotherapy. Cancer Immunol Immunother 67:551–562. https://doi.org/10.1007/s00262-017-2109-5 CrossRefPubMed

Huang CY, Chiang SF, Ke TW, Chen TW, You YS, Chen WT, Chao KSC (2018c) Clinical significance of programmed death 1 ligand-1 (CD274/PD-L1) and intra-tumoral CD8+ T-cell infiltration in stage II–III colorectal cancer. Sci Rep 8:15658. https://doi.org/10.1038/s41598-018-33927-5 CrossRefPubMedPubMedCentral

Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ (2009) Cancer statistics, 2009. CA Cancer J Clin 59:225–249. https://doi.org/10.3322/caac.20006 CrossRefPubMed

Jomrich G, Silberhumer GR, Marian B, Beer A, Mullauer L (2016) Programmed death-ligand 1 expression in rectal cancer. Eur Surg 48:352–356. https://doi.org/10.1007/s10353-016-0447-8 CrossRefPubMedPubMedCentral

Keir ME, Butte MJ, Freeman GJ, Sharpe AH (2008) PD-1 and its ligands in tolerance and immunity. Annu Rev Immunol 26:677–704. https://doi.org/10.1146/annurev.immunol.26.021607.090331 CrossRefPubMed

Kim JH, Park HE, Cho NY, Lee HS, Kang GH (2016) Characterisation of PD-L1-positive subsets of microsatellite-unstable colorectal cancers. Br J Cancer 115:490–496. https://doi.org/10.1038/bjc.2016.211 CrossRefPubMedPubMedCentral

Lee LH et al (2016) Patterns and prognostic relevance of PD-1 and PD-L1 expression in colorectal carcinoma. Mod Pathol 29:1433–1442. https://doi.org/10.1038/modpathol.2016.139 CrossRefPubMedPubMedCentral

Lim YJ et al (2017) Chemoradiation-induced alteration of programmed death-ligand 1 and CD8+ tumor-infiltrating lymphocytes identified patients with poor prognosis in rectal cancer: a matched comparison analysis. Int J Radiat Oncol Biol Phys 99:1216–1224. https://doi.org/10.1016/j.ijrobp.2017.07.004 CrossRefPubMed

Lin TY, Fan CW, Maa MC, Leu TH (2015) Lipopolysaccharide-promoted proliferation of Caco-2 cells is mediated by c-Src induction and ERK activation. Biomedicine (Taipei) 5:5 https://doi.org/10.7603/s40681-015-0005-x CrossRef

Ogura A et al (2018) Pattern of programmed cell death-ligand 1 expression and CD8-positive T-cell infiltration before and after chemoradiotherapy in rectal cancer European. J Cancer 91:11–20. https://doi.org/10.1016/j.ejca.2017.12.005 CrossRef

Phipps AI et al (2015) Association between molecular subtypes of colorectal cancer and patient survival. Gastroenterology 148:77–87.e72. https://doi.org/10.1053/j.gastro.2014.09.038 CrossRefPubMed

Pol J et al (2015) Trial Watch: immunogenic cell death inducers for anticancer chemotherapy. Oncoimmunology 4:e1008866. https://doi.org/10.1080/2162402X.2015.1008866 CrossRefPubMedPubMedCentral

Rodel C et al (2005) Prognostic significance of tumor regression after preoperative chemoradiotherapy for rectal cancer. J Clin Oncol 23:8688–8696. https://doi.org/10.1200/JCO.2005.02.1329 CrossRefPubMed

Sabatier R et al (2015) Prognostic and predictive value of PDL1 expression in breast cancer. Oncotarget 6:5449–5464. https://doi.org/10.18632/oncotarget.3216 CrossRefPubMed

Saigusa S et al (2016) Implication of programmed cell death ligand 1 expression in tumor recurrence and prognosis in rectal cancer with neoadjuvant chemoradiotherapy. Int J Clin Oncol 21:946–952. https://doi.org/10.1007/s10147-016-0962-4 CrossRefPubMed

Sauer R et al (2012) Preoperative versus postoperative chemoradiotherapy for locally advanced rectal cancer: results of the German CAO/ARO/AIO-94 randomized phase III trial after a median follow-up of 11 years. J Clin Oncol 30:1926–1933. https://doi.org/10.1200/JCO.2011.40.1836 CrossRefPubMed

Schalper KA, Velcheti V, Carvajal D, Wimberly H, Brown J, Pusztai L, Rimm DL (2014) In situ tumor PD-L1 mRNA expression is associated with increased TILs and better outcome in breast carcinomas. Clin Cancer Res 20:2773–2782. https://doi.org/10.1158/1078-0432.CCR-13-2702 CrossRefPubMed

Showalter A, Limaye A, Oyer JL, Igarashi R, Kittipatarin C, Copik AJ, Khaled AR (2017) Cytokines in immunogenic cell death: applications for cancer immunotherapy. Cytokine 97:123–132. https://doi.org/10.1016/j.cyto.2017.05.024 CrossRefPubMedPubMedCentral

Smyth MJ, Ngiow SF, Ribas A, Teng MWL (2015) Combination cancer immunotherapies tailored to the tumour microenvironment. Nat Rev Clin Oncol 13:143–158. https://doi.org/10.1038/nrclinonc.2015.209 CrossRefPubMed

Spranger S, Spaapen RM, Zha Y, Williams J, Meng Y, Ha TT, Gajewski TF (2013) Up-regulation of PD-L1, IDO, and T(regs) in the melanoma tumor microenvironment is driven by CD8(+) T cells. Sci Transl Med 5:200ra116. https://doi.org/10.1126/scitranslmed.3006504 CrossRefPubMedPubMedCentral

Taube JM et al (2012) Colocalization of inflammatory response with B7-h1 expression in human melanocytic lesions supports an adaptive resistance mechanism of immune escape. Sci Transl Med 4:127ra137. https://doi.org/10.1126/scitranslmed.3003689 CrossRef

Teng MWL, Ngiow SF, Ribas A, Smyth MJ (2015) Classifying cancers based on T-cell infiltration and PD-L1. Cancer Res 75:2139–2145. https://doi.org/10.1158/0008-5472.can-15-0255 CrossRefPubMedPubMedCentral

Thompson RH et al (2006) Tumor B7-H1 is associated with poor prognosis in renal cell carcinoma patients with long-term follow-up. Cancer Res 66:3381–3385. https://doi.org/10.1158/0008-5472.CAN-05-4303 CrossRefPubMed

Topalian SL et al (2012) Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med 366:2443–2454. https://doi.org/10.1056/NEJMoa1200690 CrossRefPubMedPubMedCentral

Velcheti V et al (2014) Programmed death ligand-1 expression in non-small cell lung cancer. Lab Invest 94:107–116. https://doi.org/10.1038/labinvest.2013.130 CrossRefPubMed

Wang X, Teng F, Kong L, Yu J (2016) PD-L1 expression in human cancers and its association with clinical outcomes. Onco Targets Ther 9:5023–5039. https://doi.org/10.2147/OTT.S105862 CrossRefPubMedPubMedCentral

Wang X et al (2018) RSF-1 overexpression determines cancer progression and drug resistance in cervical cancer. Biomedicine (Taipei) 8:4. https://doi.org/10.1051/bmdcn/2018080104 CrossRef

Wennerberg E, Vanpouille-Box C, Bornstein S, Yamazaki T, Demaria S, Galluzzi L (2017) Immune recognition of irradiated cancer cells. Immunol Rev 280:220–230. https://doi.org/10.1111/imr.12568 CrossRefPubMedPubMedCentral

Xiao Y, Freeman GJ (2015) The microsatellite instable subset of colorectal cancer is a particularly good candidate for checkpoint blockade. Immunother Cancer Discov 5:16–18. https://doi.org/10.1158/2159-8290.cd-14-1397 CrossRef

Yoon WH, Kim HJ, Kim CH, Joo JK, Kim YJ, Kim HR (2015) Oncologic impact of pathologic response on clinical outcome after preoperative chemoradiotherapy in locally advanced rectal cancer. Ann Surg Treat Res 88:15–20. https://doi.org/10.4174/astr.2015.88.1.15 CrossRefPubMed

Titel: Prognostic relevance of programmed cell death-ligand 1 expression and CD8+ TILs in rectal cancer patients before and after neoadjuvant chemoradiotherapy
verfasst von: Tsung-Wei Chen
Kevin Chih-Yang Huang
Shu-Fen Chiang
William Tzu-Liang Chen
Tao-Wei Ke
K. S. Clifford Chao
Publikationsdatum: 14.03.2019
Verlag: Springer Berlin Heidelberg
Erschienen in: Journal of Cancer Research and Clinical Oncology / Ausgabe 4/2019
Print ISSN: 0171-5216
Elektronische ISSN: 1432-1335
DOI: https://doi.org/10.1007/s00432-019-02874-7

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Prognostic relevance of programmed cell death-ligand 1 expression and CD8+ TILs in rectal cancer patients before and after neoadjuvant chemoradiotherapy

Abstract

Purpose/background

Materials and methods

Results

Conclusion

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Conclusion

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