Einzeltreffer — DigiBib

Background: Penile squamous cell carcinoma (PSCC) is a human papillomavirus (HPV)-associated malignancy. Immunotherapy is emerging as a potential treatment for advanced PSCC. In this study, the authors analyzed the association of HPV status with outcomes and the immune microenvironment in patients with advanced PSCC undergoing programmed cell death protein 1 (PD1) inhibitor-based combination therapy (PCT).

Methods: HPV status was assessed using quantitative polymerase chain reaction in 87 patients with advanced PSCC treated with PCT. Objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) in the HPV+ and HPV- groups were compared. Additionally, bulk RNA sequencing was performed to investigate the potential impact of HPV on the immune microenvironment in advanced PSCC.

Results: Among patients receiving first-line PCT, ORR (91.7% vs. 64.6%, p = .014) and DCR (100.0% vs. 79.2%, p = .025) in the HPV+ group were higher compared to the HPV- group. Kaplan-Meier curves demonstrated that the HPV+ group exhibited superior PFS (p = .005) and OS (p = .004) for patients in the first-line setting. However, these advantages of HPV infection were not observed in multi-line PCT (p > .050). HPV status remained an independent prognostic factor for predicting better ORR (p = .024), PFS (p = .002), and OS (p = .020) in the multivariate analyses. Landmark analyses showed that the HPV-induced superiority of PFS occurred at an early stage (within 3 months) and OS occurred at a relatively late stage (within 9 months). Bioinformatic analyses identified potential immune-activated genes (GLDC, CYP4F12, etc.) and pathways (RAGE, PI3K/AKT, etc.), antitumor immune cell subtypes, and lower tumor immune dysfunction and exclusion scores in HPV+ tissues.

Conclusions: HPV infection may confer treatment efficacy and survival benefits in patients with advanced PSCC receiving first-line PCT because of the possible stimulation of the antitumor immune microenvironment.

Plain Language Summary: Human papillomavirus (HPV) infection may induce better objective response rate, progression-free survival (PFS), and overall survival (OS) for advanced penile squamous cell carcinoma (PSCC) patients receiving first-line programmed cell death protein 1 inhibitor-based combination therapy (PCT) instead of multi-line PCT. HPV infection-induced PFS advantage occurs at an early stage (within 3 months) whereas OS superiority occurs at a relatively late stage (within 9 months). Antitumor immune microenvironment could be stimulated by HPV infection in advanced PSCC tissues.

Titel:	Human papillomavirus infection affects treatment outcomes and the immune microenvironment in patients with advanced penile squamous cell carcinoma receiving programmed cell death protein 1 inhibitor-based combination therapy.
Autor/in / Beteiligte Person:	Wei, L ; Li, Z ; Guo, S ; Ma, H ; Shi, Y ; An, X ; Huang, K ; Xiong, L ; Xue, T ; Zhang, Z ; Yao, K ; Luo, J ; Han, H
Link:	Full Text Finder (Volltext)
Zeitschrift:	Cancer, Jg. 130 (2024-05-01), Heft 9, S. 1650-1662
Veröffentlichung:	<2005- >: Hoboken, NJ : Wiley ; <i>Original Publication</i>: New York [etc.] Published for the American Cancer Society by J. Wiley [etc.], 2024
Medientyp:	academicJournal
ISSN:	1097-0142 (electronic)
DOI:	10.1002/cncr.35177
Schlagwort:	Male Humans Immune Checkpoint Inhibitors therapeutic use Phosphatidylinositol 3-Kinases Treatment Outcome Tumor Microenvironment Papillomavirus Infections complications Carcinoma, Squamous Cell pathology Penile Neoplasms drug therapy
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article Language: English [Cancer] 2024 May 01; Vol. 130 (9), pp. 1650-1662. <i>Date of Electronic Publication: </i>2023 Dec 29. MeSH Terms: Papillomavirus Infections* / complications ; Carcinoma, Squamous Cell* / pathology ; Penile Neoplasms* / drug therapy ; Male ; Humans ; Immune Checkpoint Inhibitors / therapeutic use ; Phosphatidylinositol 3-Kinases ; Treatment Outcome ; Tumor Microenvironment References: Sung H, Ferlay J, Siegel RL, et al. Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209‐249. doi:10.3322/caac.21660. ; Sharma P, Spiess PE. Penile cancer: advanced penile cancer continues to elude systemic therapy. Nat Rev Urol. 2015;12(4):185‐186. doi:10.1038/nrurol.2015.30. ; El Zarif T, Nassar AH, Pond GR, et al. Safety and efficacy of immune checkpoint inhibitors in advanced penile cancer: report from the Global Society of Rare Genitourinary Tumors. J Natl Cancer Inst. 2023:115(12):1605‐1615. ; de Vries HM, Rafael TS, Gil‐Jimenez A, et al. Atezolizumab with or without radiotherapy for advanced squamous cell carcinoma of the penis (the PERICLES study): a phase II trial. J Clin Oncol. 2023:41(31):4872‐4880. ; Yan R, Ma H, Jiang L, et al. First‐line programmed death receptor‐1 (PD‐1) inhibitor and epidermal growth factor receptor (EGFR) blockade, combined with platinum‐based chemotherapy, for stage IV penile cancer. BJU Int. 2023;131(2):198‐207. doi:10.1111/bju.15828. ; Olesen TB, Sand FL, Rasmussen CL, et al. Prevalence of human papillomavirus DNA and p16INK4a in penile cancer and penile intraepithelial neoplasia: a systematic review and meta‐analysis. Lancet Oncol. 2019;20(1):145‐158. doi:10.1016/s1470‐2045(18)30682‐x. ; Urinary and male genital tumours. WHO Classification of Tumours, 5th ed. Vol. 8. IARC; 2022. ; Yuan Z, Naghavi AO, Tang D, et al. The relationship between HPV status and chemoradiotherapy in the locoregional control of penile cancer. World J Urol. 2018;36(9):1431‐1440. doi:10.1007/s00345‐018‐2280‐0. ; Zandberg DP, Algazi AP, Jimeno A, et al. Durvalumab for recurrent or metastatic head and neck squamous cell carcinoma: results from a single‐arm, phase II study in patients with ≥25% tumour cell PD‐L1 expression who have progressed on platinum‐based chemotherapy. Eur J Cancer. 2019;107:142‐152. doi:10.1016/j.ejca.2018.11.015. ; Chu C, Yao K, Lu J, et al. Immunophenotypes based on the tumor immune microenvironment allow for unsupervised penile cancer patient stratification. Cancers. 2020;12(7):1796. doi:10.3390/cancers12071796. ; Nazha B, Zhuang T, Wu S, et al. Comprehensive genomic profiling of penile squamous cell carcinoma and the impact of human papillomavirus status on immune‐checkpoint inhibitor‐related biomarkers. Cancer. 2023:129(24):3884‐3893. ; Maeng M, Tilsted HH, Jensen LO, et al. Differential clinical outcomes after 1 year versus 5 years in a randomised comparison of zotarolimus‐eluting and sirolimus‐eluting coronary stents (the SORT OUT III study): a multicentre, open‐label, randomised superiority trial. Lancet. 2014;383(9934):2047‐2056. doi:10.1016/s0140‐6736(14)60405‐0. ; Chu C, Chen K, Tan X, et al. Prevalence of human papillomavirus and implication on survival in Chinese penile cancer. Virchows Arch. 2020;477(5):667‐675. doi:10.1007/s00428‐020‐02831‐7. ; Huang KB, Guo SJ, Li YH, et al. Genome‐wide profiling reveals HPV integration pattern and activated carcinogenic pathways in penile squamous cell carcinoma. Cancers. 2021;13(23):6104. doi:10.3390/cancers13236104. ; Wang B, Gu W, Wan F, et al. Prognosis of the 8th TNM staging system for penile cancer and refinement of prognostication by incorporating high risk human papillomavirus status. J Urol. 2020;203(3):562‐569. doi:10.1097/ju.0000000000000584. ; Ferris RL, Blumenschein G Jr, Fayette J, et al. Nivolumab vs investigator's choice in recurrent or metastatic squamous cell carcinoma of the head and neck: 2‐year long‐term survival update of CheckMate 141 with analyses by tumor PD‐L1 expression. Oral Oncol. 2018;81:45‐51. doi:10.1016/j.oraloncology.2018.04.008. ; Bauml J, Seiwert TY, Pfister DG, et al. Pembrolizumab for platinum‐ and cetuximab‐refractory head and neck cancer: results from a single‐arm, phase II study. J Clin Oncol. 2017;35(14):1542‐1549. doi:10.1200/jco.2016.70.1524. ; Mehra R, Seiwert TY, Gupta S, et al. Efficacy and safety of pembrolizumab in recurrent/metastatic head and neck squamous cell carcinoma: pooled analyses after long‐term follow‐up in KEYNOTE‐012. Br J Cancer. 2018;119(2):153‐159. doi:10.1038/s41416‐018‐0131‐9. ; Djajadiningrat RS, Jordanova ES, Kroon BK, et al. Human papillomavirus prevalence in invasive penile cancer and association with clinical outcome. J Urol. 2015;193(2):526‐531. doi:10.1016/j.juro.2014.08.087. ; Bandini M, Ross JS, Zhu Y, et al. Association between human papillomavirus infection and outcome of perioperative nodal radiotherapy for penile carcinoma. Eur Urol Oncol. 2021;4(5):802‐810. doi:10.1016/j.euo.2020.10.011. ; Morelli AE, Ronchetti RD, Secchi AD, Cufré MA, Paredes A, Fainboim L. Assessment by planimetry of Langerhans’ cell density in penile epithelium with human papillomavirus infection: changes observed after topical treatment. J Urol. 1992;147(5):1268‐1273. doi:10.1016/s0022‐5347(17)37538‐9. ; Lohneis P, Boral S, Kaufmann AM, et al. Human papilloma virus status of penile squamous cell carcinoma is associated with differences in tumour‐infiltrating T lymphocytes. Virchows Arch. 2014;466(3):323‐331. doi:10.1007/s00428‐014‐1713‐4. ; Xie H, Yan T, Lu X, et al. GLDC mitigated by miR‐30e regulates cell proliferation and tumor immune infiltration in TNBC. Front Immunol. 2022;13:1033367. doi:10.3389/fimmu.2022.1033367. ; Jia W, Chen S, Wei R, et al. CYP4F12 is a potential biomarker and inhibits cell migration of head and neck squamous cell carcinoma via EMT pathway. Sci Rep. 2023;13(1):10956. doi:10.1038/s41598‐023‐37950‐z. ; Reed JC, Preston‐Hurlburt P, Philbrick W, et al. The receptor for advanced glycation endproducts (RAGE) modulates T cell signaling. PLoS One. 2020;15(9):e0236921. doi:10.1371/journal.pone.0236921. ; Li P, Zhou D, Chen D, et al. Tumor‐secreted IFI35 promotes proliferation and cytotoxic activity of CD8+ T cells through PI3K/AKT/mTOR signaling pathway in colorectal cancer. J Biomed Sci. 2023;30(1):47. doi:10.1186/s12929‐023‐00930‐6. ; Bruschini S, Ciliberto G, Mancini R. The emerging role of cancer cell plasticity and cell‐cycle quiescence in immune escape. Cell Death Dis. 2020;11(6):471. doi:10.1038/s41419‐020‐2669‐8. ; Zhou Y, Xu J, Luo H, Meng X, Chen M, Zhu D. Wnt signaling pathway in cancer immunotherapy. Cancer Lett. 2022;525:84‐96. doi:10.1016/j.canlet.2021.10.034. ; Galmiche A, Rak J, Roumenina LT, Saidak Z. Coagulome and the tumor microenvironment: an actionable interplay. Trends Cancer. 2022;8(5):369‐383. doi:10.1016/j.trecan.2021.12.008. ; Haas GP, Blumenstein BA, Gagliano RG, et al. Cisplatin, methotrexate and bleomycin for the treatment of carcinoma of the penis: a Southwest Oncology Group study. J Urol. 1999;161(6):1823‐1825. doi:10.1016/s0022‐5347(05)68815‐5. ; Theodore C, Skoneczna I, Bodrogi I, et al. A phase II multicentre study of irinotecan (CPT 11) in combination with cisplatin (CDDP) in metastatic or locally advanced penile carcinoma (EORTC PROTOCOL 30992). Ann Oncol. 2008;19(7):1304‐1307. doi:10.1093/annonc/mdn149. ; Nicholson S, Hall E, Harland SJ, et al. Phase II trial of docetaxel, cisplatin and 5FU chemotherapy in locally advanced and metastatic penis cancer (CRUK/09/001). Br J Cancer. 2013;109(10):2554‐2559. doi:10.1038/bjc.2013.620. ; Pagliaro LC, Williams DL, Daliani D, et al. Neoadjuvant paclitaxel, ifosfamide, and cisplatin chemotherapy for metastatic penile cancer: a phase II study. J Clin Oncol. 2010;28(24):3851‐3857. doi:10.1200/jco.2010.29.5477. ; Necchi A, Lo Vullo S, Perrone F, et al. First‐line therapy with dacomitinib, an orally available pan‐HER tyrosine kinase inhibitor, for locally advanced or metastatic penile squamous cell carcinoma: results of an open‐label, single‐arm, single‐centre, phase 2 study. BJU Int. 2018;121(3):348‐356. doi:10.1111/bju.14013. ; Di Lorenzo G, Federico P, Buonerba C, et al. Paclitaxel in pretreated metastatic penile cancer: final results of a phase 2 study. Eur Urol. 2011;60(6):1280‐1284. doi:10.1016/j.eururo.2011.08.028. ; Ledys F, Klopfenstein Q, Truntzer C, et al. RAS status and neoadjuvant chemotherapy impact CD8+ cells and tumor HLA class I expression in liver metastatic colorectal cancer. J Immunother Cancer. 2018;6(1):123. doi:10.1186/s40425‐018‐0438‐3. ; Wang W, Green M, Choi JE, et al. CD8+ T cells regulate tumour ferroptosis during cancer immunotherapy. Nature. 2019;569(7755):270‐274. doi:10.1038/s41586‐019‐1170‐y. ; Olesch C, Sirait‐Fischer E, Berkefeld M, et al. S1PR4 ablation reduces tumor growth and improves chemotherapy via CD8+ T cell expansion. J Clin Invest. 2020;130(10):5461‐5476. doi:10.1172/jci136928. Grant Information: RCYX20221008093032008 Shenzhen Science and Technology Program; JCYJ20190807145409328 Science and Technology Planning Project of Shenzhen Municipality; 2021A1515220182 Guangdong Province Nature Foundation of China Project; 2022A1515012200 Guangdong Province Nature Foundation of China Project; 2022A1515012321 Guangdong Province Nature Foundation of China Project Contributed Indexing: Keywords: PD1 inhibitor; advanced penile squamous cell carcinoma; combination therapy; efficacy; human papillomavirus; immune microenvironment; prognosis Substance Nomenclature: 0 (Immune Checkpoint Inhibitors) ; EC 2.7.1.- (Phosphatidylinositol 3-Kinases) Entry Date(s): Date Created: 20231229 Date Completed: 20240415 Latest Revision: 20240415 Update Code: 20240415

Klicken Sie ein Format an und speichern Sie dann die Daten oder geben Sie eine Empfänger-Adresse ein und lassen Sie sich per Email zusenden.

BibTeX Citavi, JabRef, u.a.
(Literaturverwaltung)

PDF kein Volltext!
(Merkzettel, Notizen)

RIS Endnote, Citavi u.a.
(Literaturverwaltung)

MODS
(XML zur Weiterverarbeitung)

oder

Wählen Sie das für Sie passende Zitationsformat und kopieren Sie es dann in die Zwischenablage, lassen es sich per Mail zusenden oder speichern es als PDF-Datei.

Gewünschter Zitations-Stil:

oder

Bitte prüfen Sie, ob die Zitation formal korrekt ist, bevor Sie sie in einer Arbeit verwenden. Benutzen Sie gegebenenfalls den "Exportieren"-Dialog, wenn Sie ein Literaturverwaltungsprogramm verwenden und die Zitat-Angaben selbst formatieren wollen.

Human papillomavirus infection affects treatment outcomes and the immune microenvironment in patients with advanced penile squamous cell carcinoma receiving programmed cell death protein 1 inhibitor-based combination therapy.