Oropharyngeal cancer outcomes correlate with p16 status, multinucleation and immune infiltration.
Oropharyngeal cancer outcomes correlate with p16 status, multinucleation and immune infiltration.
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DOI：
10.1038/s41379-022-01024-8
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发表时间：
2022-08
期刊：
影响因子：
7.5
通讯作者：
Sandulache, Vlad C.
中科院分区：
文献类型：
--
作者：
Wilde, David C.;Castro, Patricia D.;Bera, Kaustav;Lai, Syeling;Madabhushi, Anant;Corredor, German;Koyuncu, Can;Lewis, James S., Jr.;Lu, Cheng;Frederick, Mitchell J.;Frederick, Allan M.;Haugen, Avery E.;Zevallos, Jose P.;Sturgis, Erich M.;Shi, Justin;Huang, Andrew T.;Hernandez, David J.;Skinner, Heath D.;Kemnade, Jan O.;Yu, Wendong;Sikora, Andrew G.;Sandulache, Vlad C.
口咽鳞状细胞癌（OPSCC）主要由人乳头瘤病毒（HPV）引发，具有复杂的生物学和免疫学表型。尽管HPV/p16状态可用于将OPSCC患者分层作为生存的功能，但目前尚不清楚是什么驱动了HPV相关OPSCC治疗反应的改善，以及是否存在可靶向的生物标志物，可以为精确的肿瘤学方法提供信息。我们分析了2000年至2016年期间接受治疗的OPSCC患者，并使用常规临床参数、风险参数和深度学习算法生成的相关局部区域控制（LRC）、无病生存（DFS）和总生存（OS）进行分析。深度学习算法用于量化肿瘤浸润淋巴细胞（TILs） （OP-TIL）和多核肿瘤细胞（MuNI），以及靶向转录组学。P16是LRC、DFS和OS的主要决定因素，但烟草暴露、OP-TIL和MuNI风险特征与临床结果相关，独立于P16状态，P16、OP-TIL和MuNI的组合比单个参数产生更好的OPSCC风险分层。差异基因表达（DEG）分析显示MuNI和OP-TIL之间存在重叠，并确定了与DNA修复、氧化应激反应和肿瘤免疫相关的基因是与生存最重要的相关基因。炎症/免疫途径的改变与所有风险特征和肿瘤预后密切相关。这表明，OPSCC的发展包括多种必要的和允许的致癌和免疫事件之间的交叉，这些事件可能是机制相关的。无论HPV状态如何，肿瘤免疫与OPSCC肿瘤预后之间的密切关系可能为进一步开发生物标志物和结合免疫检查点抑制剂的精确肿瘤学方法提供机会，以获得最大的抗肿瘤疗效。
Oropharyngeal squamous cell carcinoma (OPSCC), largely fueled by the human papillomavirus (HPV), has a complex biological and immunologic phenotype. Although HPV/p16 status can be used to stratify OPSCC patients as a function of survival, it remains unclear what drives an improved treatment response in HPV-associated OPSCC and whether targetable biomarkers exist that can inform a precision oncology approach. We analyzed OPSCC patients treated between 2000 and 2016 and correlated locoregional control (LRC), disease-free survival (DFS) and overall survival (OS) with conventional clinical parameters, risk parameters generated using deep-learning algorithms trained to quantify tumor-infiltrating lymphocytes (TILs) (OP-TIL) and multinucleated tumor cells (MuNI) and targeted transcriptomics. P16 was a dominant determinant of LRC, DFS and OS, but tobacco exposure, OP-TIL and MuNI risk features correlated with clinical outcomes independent of p16 status and the combination of p16, OP-TIL and MuNI generated a better stratification of OPSCC risk compared to individual parameters. Differential gene expression (DEG) analysis demonstrated overlap between MuNI and OP-TIL and identified genes involved in DNA repair, oxidative stress response and tumor immunity as the most prominent correlates with survival. Alteration of inflammatory/immune pathways correlated strongly with all risk features and oncologic outcomes. This suggests that development of OPSCC consists of an intersection between multiple required and permissive oncogenic and immunologic events which may be mechanistically linked. The strong relationship between tumor immunity and oncologic outcomes in OPSCC regardless of HPV status may provide opportunities for further biomarker development and precision oncology approaches incorporating immune checkpoint inhibitors for maximal anti-tumor efficacy.
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影响因子：
6.2
作者：
Dahlstrom, Kristina R.;Calzada, Gabriel;Hanby, Jennifer D.;Garden, Adam S.;Glisson, Bonnie S.;Li, Guojun;Roberts, Dianna B.;Weber, Randal S.;Sturgis, Erich M.
通讯作者：
Sturgis, Erich M.
影响因子：
6.4
作者：
Facompre ND;Rajagopalan P;Sahu V;Pearson AT;Montone KT;James CD;Gleber-Netto FO;Weinstein GS;Jalaly J;Lin A;Rustgi AK;Nakagawa H;Califano JA;Pickering CR;White EA;Windle BE;Morgan IM;Cohen RB;Gimotty PA;Basu D
通讯作者：
Basu D
DOI：
10.1126/science.aar3593
发表时间：
2018-10-12
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Cristescu R;Mogg R;Ayers M;Albright A;Murphy E;Yearley J;Sher X;Liu XQ;Lu H;Nebozhyn M;Zhang C;Lunceford JK;Joe A;Cheng J;Webber AL;Ibrahim N;Plimack ER;Ott PA;Seiwert TY;Ribas A;McClanahan TK;Tomassini JE;Loboda A;Kaufman D
通讯作者：
Kaufman D
影响因子：
45.3
作者：
Fakhry, Carole;Zhang, Qiang;Gillison, Maura
通讯作者：
Gillison, Maura
影响因子：
8
作者：
Gleber-Netto, Frederico O.;Rao, Xiayu;Pickering, Curtis R.
通讯作者：
Pickering, Curtis R.