{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T23:46:49Z","timestamp":1793317609781,"version":"4.5.0"},"reference-count":31,"publisher":"Elsevier BV","issue":"5","license":[{"start":{"date-parts":[[2017,5,1]],"date-time":"2017-05-01T00:00:00Z","timestamp":1493596800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2019,11,4]],"date-time":"2019-11-04T00:00:00Z","timestamp":1572825600000},"content-version":"vor","delay-in-days":917,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of Oncology"],"published-print":{"date-parts":[[2017,5]]},"DOI":"10.1093\/annonc\/mdx029","type":"journal-article","created":{"date-parts":[[2017,2,7]],"date-time":"2017-02-07T01:31:21Z","timestamp":1486431081000},"page":"1036-1041","source":"Crossref","is-referenced-by-count":224,"title":["Safety and antitumor activity of the anti-PD-1 antibody pembrolizumab in patients with recurrent carcinoma of the anal canal"],"prefix":"10.1016","volume":"28","author":[{"given":"P.A.","family":"Ott","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.A.","family":"Piha-Paul","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.","family":"Munster","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.J.","family":"Pishvaian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.M.J.","family":"van Brummelen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.B.","family":"Cohen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Gomez-Roca","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Ejadi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Stein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.","family":"Chan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Simonelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Morosky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Saraf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.","family":"Emancipator","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Koshiji","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Bennouna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1093\/annonc\/mdx029_bb0010","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1071\/SH12070","article-title":"The epidemiology of anal cancer","volume":"9","author":"Grulich","year":"2012","journal-title":"Sex Heal"},{"key":"10.1093\/annonc\/mdx029_bb0015","doi-asserted-by":"crossref","first-page":"1626","DOI":"10.1002\/ijc.24116","article-title":"Prevalence and type distribution of human papillomavirus in carcinoma and intraepithelial neoplasia of the vulva, vagina and anus: a meta-analysis","volume":"124","author":"De Vuyst","year":"2009","journal-title":"Int J Cancer"},{"key":"10.1093\/annonc\/mdx029_bb0020","doi-asserted-by":"crossref","first-page":"2040","DOI":"10.1200\/JCO.1997.15.5.2040","volume":"15","author":"Bartelink","year":"1997","journal-title":"J Clin Oncol"},{"key":"10.1093\/annonc\/mdx029_bb0025","doi-asserted-by":"crossref","first-page":"2527","DOI":"10.1200\/JCO.1996.14.9.2527","article-title":"Role of mitomycin in combination with fluorouracil and radiotherapy, and of salvage chemoradiation in the definitive nonsurgical treatment of epidermoid carcinoma of the anal canal: results of a phase III randomized intergroup study","volume":"14","author":"Flam","year":"1996","journal-title":"J Clin Oncol"},{"key":"10.1093\/annonc\/mdx029_bb0030","doi-asserted-by":"crossref","first-page":"1914","DOI":"10.1001\/jama.299.16.1914","article-title":"Fluorouracil, mitomycin, and radiotherapy vs fluorouracil, cisplatin, and radiotherapy for carcinoma of the anal canal: a randomized controlled trial","volume":"299","author":"Ajani","year":"2008","journal-title":"JAMA"},{"key":"10.1093\/annonc\/mdx029_bb0035","unstructured":"National Comprehensive Cancer Network, Inc.: NCCN Clinical Practice Guidelines in Oncology. Anal Carcinoma v.1 2017. 2016.https:\/\/www.nccn.org\/professionals\/physician_gls\/pdf\/anal.pdf (24 October 2016, date last accessed)."},{"key":"10.1093\/annonc\/mdx029_bb0040","doi-asserted-by":"crossref","first-page":"200ra116","DOI":"10.1126\/scitranslmed.3006504","article-title":"Up-regulation of PD-L1, IDO, and Tregs in the melanoma tumor microenvironment is driven by CD8+ T cells","volume":"5","author":"Spranger","year":"2013","journal-title":"Sci Transl Med"},{"key":"10.1093\/annonc\/mdx029_bb0045","doi-asserted-by":"crossref","first-page":"127ra37.","DOI":"10.1126\/scitranslmed.3003689","article-title":"Colocalization of inflammatory response with B7-H1 expression in human melanocytic lesions supports an adaptive resistance mechanism of immune escape","volume":"4","author":"Taube","year":"2012","journal-title":"Sci Transl Med"},{"key":"10.1093\/annonc\/mdx029_bb0050","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1126\/science.aaa8172","article-title":"The future of immune checkpoint therapy","volume":"348","author":"Sharma","year":"2015","journal-title":"Science"},{"key":"10.1093\/annonc\/mdx029_bb0055","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1038\/nature13904","article-title":"MPDL3280A (anti-PD-L1) treatment leads to clinical activity in metastatic bladder cancer","volume":"515","author":"Powles","year":"2014","journal-title":"Nature"},{"key":"10.1093\/annonc\/mdx029_bb0060","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1016\/S1470-2045(16)00175-3","article-title":"Pembrolizumab for patients with PD-L1-positive advanced gastric cancer (KEYNOTE-012): a multicentre, open-label, phase 1b trial","volume":"17","author":"Muro","year":"2016","journal-title":"Lancet Oncol"},{"key":"10.1093\/annonc\/mdx029_bb0065","doi-asserted-by":"crossref","first-page":"2443","DOI":"10.1056\/NEJMoa1200690","article-title":"Safety, activity, and immune correlates of anti-PD-1 antibody in cancer","volume":"366","author":"Topalian","year":"2012","journal-title":"N Engl J Med"},{"key":"10.1093\/annonc\/mdx029_bb0070","doi-asserted-by":"crossref","first-page":"2018","DOI":"10.1056\/NEJMoa1501824","article-title":"for the KEYNOTE-001 Investigators: Pembrolizumab for the treatment of non-small-cell lung cancer","volume":"372","author":"Garon","year":"2015","journal-title":"N Engl J Med"},{"key":"10.1093\/annonc\/mdx029_bb0075","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1056\/NEJMoa1504030","article-title":"Combined nivolumab and ipilimumab or monotherapy in untreated melanoma","volume":"373","author":"Larkin","year":"2015","journal-title":"N Engl J Med"},{"key":"10.1093\/annonc\/mdx029_bb0080","doi-asserted-by":"crossref","first-page":"1259","DOI":"10.5858\/arpa.2015-0544-OA","article-title":"Development of a prototype immunohistochemistry assay to measure programmed death ligand-1 expression in tumor tissue","volume":"140","author":"Dolled-Filhart","year":"2016","journal-title":"Arch Pathol Lab Med"},{"key":"10.1093\/annonc\/mdx029_bb0085","doi-asserted-by":"crossref","first-page":"4431","DOI":"10.1158\/1078-0432.CCR-14-3341","article-title":"Targeting of HPV-16+ epithelial cancer cells by TCR gene engineered T cells directed against E6","volume":"21","author":"Draper","year":"2015","journal-title":"Clin Cancer Res"},{"key":"10.1093\/annonc\/mdx029_bb0090","doi-asserted-by":"crossref","first-page":"E74","DOI":"10.1002\/ijc.26497","article-title":"Systemic and local human papillomavirus 16-specific T-cell immunity in patients with head and neck cancer","volume":"131","author":"Heusinkveld","year":"2012","journal-title":"Int J Cancer"},{"key":"10.1093\/annonc\/mdx029_bb0095","doi-asserted-by":"crossref","first-page":"1733","DOI":"10.1158\/0008-5472.CAN-12-2384","article-title":"Evidence for a role of the PD-1:PD-L1 pathway in immune resistance of HPV-associated head and neck squamous cell carcinoma","volume":"73","author":"Lyford-Pike","year":"2013","journal-title":"Cancer Res"},{"key":"10.1093\/annonc\/mdx029_bb0100","doi-asserted-by":"crossref","first-page":"e965570.","DOI":"10.4161\/21624011.2014.965570","article-title":"Distinct patterns of intratumoral immune cell infiltrates in patients with HPV-associated compared to non-virally induced head and neck squamous cell carcinoma","volume":"4","author":"Partlov\u00e1","year":"2015","journal-title":"Oncoimmunology"},{"key":"10.1093\/annonc\/mdx029_bb0105","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1038\/nature14404","article-title":"Melanoma-intrinsic \u03b2-catenin signalling prevents anti-tumour immunity","volume":"523","author":"Spranger","year":"2015","journal-title":"Nature"},{"issue":"Suppl","key":"10.1093\/annonc\/mdx029_bb0110","article-title":"Association of response to programmed death receptor 1 (PD-1) blockade with pembrolizumab (MK-3475) with an interferon-inflammatory immune gene signature","volume":"33","author":"Ribas","year":"2015","journal-title":"J Clin Oncol"},{"issue":"Suppl","key":"10.1093\/annonc\/mdx029_bb0115","article-title":"Inflamed-phenotype gene expression signatures to predict benefit from the anti-PD-1 antibody pembrolizumab in PD-L1+ head and neck cancer patients","volume":"33","author":"Seiwert","year":"2015","journal-title":"J Clin Oncol"},{"issue":"Suppl","key":"10.1093\/annonc\/mdx029_bb0120","article-title":"Correlation of gene expression signatures and clinical outcomes in patients with advanced gastric cancer treated with pembrolizumab (MK-3475)","volume":"33","author":"Shankaran","year":"2015","journal-title":"J Clin Oncol"},{"key":"10.1093\/annonc\/mdx029_bb0125","doi-asserted-by":"crossref","unstructured":"Morris VK, Mahvash A, Vence L et al. NCI#9673 phase II study of nivolumab in refractory metastatic squamous cell carcinoma of the anal canal: immunologic correlates of response. Presented at the American Association for Cancer Research Annual Meeting, New Orleans, LA, 16\u201320 April 2016.","DOI":"10.1158\/1538-7445.AM2016-CT131"},{"key":"10.1093\/annonc\/mdx029_bb0130","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1126\/science.aaa1348","article-title":"Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer","volume":"348","author":"Rizvi","year":"2015","journal-title":"Science"},{"key":"10.1093\/annonc\/mdx029_bb0135","doi-asserted-by":"crossref","first-page":"2189","DOI":"10.1056\/NEJMoa1406498","article-title":"Genetic basis for clinical response to CTLA-4 blockade in melanoma","volume":"371","author":"Snyder","year":"2014","journal-title":"N Engl J Med"},{"key":"10.1093\/annonc\/mdx029_bb0140","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1126\/science.aad0095","article-title":"Genomic correlates of response to CTLA-4 blockade in metastatic melanoma","volume":"350","author":"Van Allen","year":"2015","journal-title":"Science"},{"key":"10.1093\/annonc\/mdx029_bb0145","doi-asserted-by":"crossref","first-page":"2509","DOI":"10.1056\/NEJMoa1500596","article-title":"PD-1 blockade in tumors with mismatch-repair deficiency","volume":"372","author":"Le","year":"2015","journal-title":"N Engl J Med"},{"key":"10.1093\/annonc\/mdx029_bb0150","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1038\/nature14129","article-title":"The Cancer Genome Atlas Network: Comprehensive genomic characterization of head and neck squamous cell carcinomas","volume":"517","year":"2015","journal-title":"Nature"},{"key":"10.1093\/annonc\/mdx029_bb0155","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1038\/nature12881","article-title":"Landscape of genomic alterations in cervical carcinomas","volume":"506","author":"Ojesina","year":"2014","journal-title":"Nature"},{"key":"10.1093\/annonc\/mdx029_bb0160","doi-asserted-by":"crossref","first-page":"1336","DOI":"10.1093\/annonc\/mdw152","article-title":"Comprehensive genomic profiling of anal squamous cell carcinoma reveals distinct genomically defined classes","volume":"27","author":"Chung","year":"2016","journal-title":"Ann Oncol"}],"container-title":["Annals of Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0923753419320083?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0923753419320083?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/academic.oup.com\/annonc\/article-pdf\/28\/5\/1036\/24169345\/mdx029.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,6,26]],"date-time":"2021-06-26T04:15:07Z","timestamp":1624680907000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0923753419320083"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,5]]},"references-count":31,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2017,5]]}},"alternative-id":["S0923753419320083"],"URL":"https:\/\/doi.org\/10.1093\/annonc\/mdx029","relation":{},"ISSN":["0923-7534"],"issn-type":[{"value":"0923-7534","type":"print"}],"subject":[],"published":{"date-parts":[[2017,5]]}}}