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European Surgery
Published in: European Surgery 6/2016

Open Access 01-12-2016 | original article

Programmed death-ligand 1 expression in rectal cancer

Authors: G. Jomrich, G. R. Silberhumer, B. Marian, A. Beer, L. Müllauer

Published in: European Surgery | Issue 6/2016

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Summary

Background

Colorectal cancer (CRC) is the fourth most common cause of death worldwide. Approximately 30 % of all CRC occurs in the rectum. Improvements in survival rates were achieved thanks to multimodal therapy, combining surgery and chemoradiation. Nevertheless, the prognosis of patients suffering from rectal cancer (RC) remains poor. Programmed cell death protein 1 (PD-1) and its ligand programmed death ligand 1 (PD-L1) regulate tumor immune response. The aim of this study was to analyze the expression of PD-L1 in RC pre- and post-neoadjuvant therapy and evaluate PD-L1 as a biomarker and potential target for therapy.

Methods

In all, 29 patients with RC treated at the Medical University Vienna who received preoperative chemoradiation were retrospectively enrolled in this study. Expression of PD-L1 was investigated by immunohistochemistry with two different anti-PD-L1 antibodies.

Results

No PD-L1 expression on cancer cells could be observed in all 29 cases in the specimens before chemoradiation as well as in the surgical specimens after neoadjuvant therapy. In one of the two staining methods performed, five (17.24 %) post-chemoradiation cases showed faint lymphohistiocytic staining.

Conclusion

No expression of PD-L1 in RC cells before and after chemoradiation was found in our collective of 29 patients. Further investigations to evaluate the role of PD-L1 as a potential therapeutic target in RC are urgently needed.
Literature
1.
Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015;136(5):E359–E386.CrossRefPubMed
2.
Sauer R, Becker H, Hohenberger W, Rodel C, Wittekind C, Fietkau R, et al. Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med. 2004;351(17):1731–40.CrossRefPubMed
3.
Derbel O, Wang Q, Desseigne F, Rivoire M, Meeus P, Peyrat P, et al. Impact of KRAS, BRAF and PI3KCA mutations in rectal carcinomas treated with neoadjuvant radiochemotherapy and surgery. BMC Cancer. 2013;13:200.CrossRefPubMedPubMedCentral
4.
Swaika A, Hammond WA, Joseph RW. Current state of anti-PD-L1 and anti-PD-1 agents in cancer therapy. Mol Immunol. 2015;67(2 Pt A):4–17.CrossRefPubMed
5.
Gao Q, Wang XY, Qiu SJ, Yamato I, Sho M, Nakajima Y, et al. Overexpression of PD-L1 significantly associates with tumor aggressiveness and postoperative recurrence in human hepatocellular carcinoma. Clin Cancer Res. 2009;15(3):971–9.CrossRefPubMed
6.
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(21):2018–28.CrossRefPubMed
7.
Topalian SL, Hodi FS, Brahmer JR, Gettinger SN, Smith DC, McDermott DF, et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med. 2012;366(26):2443–54.CrossRefPubMedPubMedCentral
8.
Dong H, Strome SE, Salomao DR, Tamura H, Hirano F, Flies DB, et al. Tumor-associated B7-H1 promotes T‑cell apoptosis: a potential mechanism of immune evasion. Nat Med. 2002;8(8):793–800.PubMed
9.
Freeman GJ, Long AJ, Iwai Y, Bourque K, Chernova T, Nishimura H, et al. Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation. J Exp Med. 2000;192(7):1027–34.CrossRefPubMedPubMedCentral
10.
11.
Ramsay AG. Immune checkpoint blockade immunotherapy to activate anti-tumour T‑cell immunity. Br J Haematol. 2013;162(3):313–25.CrossRefPubMed
12.
Li J, Jie HB, Lei Y, Gildener-Leapman N, Trivedi S, Green T, et al. PD-1/SHP-2 inhibits Tc1/Th1 phenotypic responses and the activation of T cells in the tumor microenvironment. Cancer Res. 2015;75(3):508–18.CrossRefPubMed
13.
Spranger S, Spaapen RM, Zha Y, Williams J, Meng Y, Ha TT, et al. Up-regulation of PD-L1, IDO, and T(regs) in the melanoma tumor microenvironment is driven by CD8(+) T cells. Sci Transl Med. 2013;5(200):200ra116.CrossRefPubMedPubMedCentral
14.
Thompson RH, Gillett MD, Cheville JC, Lohse CM, Dong H, Webster WS, et al. Costimulatory molecule B7-H1 in primary and metastatic clear cell renal cell carcinoma. Cancer. 2005;104(10):2084–91.CrossRefPubMed
15.
Velcheti V, Schalper KA, Carvajal DE, Anagnostou VK, Syrigos KN, Sznol M, et al. Programmed death ligand-1 expression in non-small cell lung cancer. Lab Invest. 2014;94(1):107–16.CrossRefPubMed
16.
Ohigashi Y, Sho M, Yamada Y, Tsurui Y, Hamada K, Ikeda N, et al. Clinical significance of programmed death-1 ligand-1 and programmed death-1 ligand-2 expression in human esophageal cancer. Clin Cancer Res. 2005;11(8):2947–53.CrossRefPubMed
17.
Wintterle S, Schreiner B, Mitsdoerffer M, Schneider D, Chen L, Meyermann R, et al. Expression of the B7-related molecule B7-H1 by glioma cells: a potential mechanism of immune paralysis. Cancer Res. 2003;63(21):7462–7.PubMed
18.
Taube JM, Anders RA, Young GD, Xu H, Sharma R, McMiller TL, et al. Colocalization of inflammatory response with B7-h1 expression in human melanocytic lesions supports an adaptive resistance mechanism of immune escape. Sci Transl Med. 2012;4(127):127ra37.CrossRefPubMedPubMedCentral
19.
Brahmer JR, Drake CG, Wollner I, Powderly JD, Picus J, Sharfman WH, et al. Phase I study of single-agent anti-programmed death-1 (MDX-1106) in refractory solid tumors: safety, clinical activity, pharmacodynamics, and immunologic correlates. J Clin Oncol. 2010;28(19):3167–75.CrossRefPubMedPubMedCentral
20.
Brahmer JR, Tykodi SS, Chow LQ, Hwu WJ, Topalian SL, Hwu P, et al. Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Engl J Med. 2012;366(26):2455–65.CrossRefPubMedPubMedCentral
21.
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
22.
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
23.
Wimberly H, Brown JR, Schalper K, Haack H, Silver MR, Nixon C, et al. PD-L1 expression correlates with tumor-infiltrating lymphocytes and response to neoadjuvant chemotherapy in breast cancer. Cancer Immunol Res. 2015;3(4):326–32.CrossRefPubMed
24.
Sobin LH, Wittekind C. International Union Against Cancer (UICC) TNM classification of malignant tumors, 7th ed. 2009.
25.
Dworak O, Keilholz L, Hoffmann A. Pathological features of rectal cancer after preoperative radiochemotherapy. Int J Colorectal Dis. 1997;12(1):19–23.CrossRefPubMed
26.
27.
Vennepureddy A, Thumallapally N, Motilal Nehru V, Atallah JP, Terjanian T. Novel drugs and combination therapies for the treatment of metastatic melanoma. J Clin Med Res. 2016;8(2):63–75.CrossRefPubMed
28.
Zhou C, Yao LD. Strategies to improve outcomes of patients with EGRF-mutant non-small cell lung cancer: review of the literature. J Thorac Oncol. 2016;11(2):174–86.CrossRefPubMed
29.
Droeser RA, Hirt C, Viehl CT, Frey DM, Nebiker C, Huber X, et al. Clinical impact of programmed cell death ligand 1 expression in colorectal cancer. Eur J Cancer. 2013;49(9):2233–42.CrossRefPubMed
30.
Xiao Y, Freeman GJ. The microsatellite instable subset of colorectal cancer is a particularly good candidate for checkpoint blockade immunotherapy. Cancer Discov. 2015;5(1):16–8.CrossRefPubMedPubMedCentral
31.
Devaraj B, Lee A, Cabrera BL, Miyai K, Luo L, Ramamoorthy S, et al. Relationship of EMAST and microsatellite instability among patients with rectal cancer. J Gastrointest Surg. 2010;14(10):1521–8.CrossRefPubMedPubMedCentral
Metadata
Title
Programmed death-ligand 1 expression in rectal cancer
Authors
G. Jomrich
G. R. Silberhumer
B. Marian
A. Beer
L. Müllauer
Publication date
01-12-2016
Publisher
Springer Vienna
Published in
European Surgery / Issue 6/2016
Print ISSN: 1682-8631
Electronic ISSN: 1682-4016
DOI
https://doi.org/10.1007/s10353-016-0447-8

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