Infiltrating lymphocytes and human papillomavirus-16--associated oropharyngeal cancer.
Infiltrating lymphocytes and human papillomavirus-16--associated oropharyngeal cancer.
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DOI：
10.1002/lary.22133
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发表时间：
2012-01
期刊：
影响因子：
2.6
通讯作者：
Wolf, Gregory
中科院分区：
文献类型：
--
作者：
Wansom, Derrick;Light, Emily;Thomas, Dafydd;Worden, Francis;Prince, Mark;Urba, Susan;Chepeha, Douglas;Kumar, Bhavna;Cordell, Kitrina;Eisbruch, Avraham;Taylor, Jeremy;Moyer, Jeffrey;Bradford, Carol;D'Silva, Nisha;Carey, Thomas;McHugh, Jonathan;Wolf, Gregory
关键词：
人乳头瘤病毒-16（HPV-16）相关的口咽鳞癌预后良好。HPV-16阳性癌症患者外周血CD 8 + T淋巴细胞水平升高，与化疗反应和生存率相关。在来自前瞻性患者队列的治疗前活检中评估肿瘤浸润淋巴细胞亚群（TIL），以确定TIL亚群是否因HPV状态、临床因素、患者结局而不同或与外周血T细胞水平相关。通过免疫组织化学在从患有晚期口咽癌的患者（n=46）产生的组织微阵列中测量CD 8、CD 4、CD 68和Treg（FoxP 3）淋巴细胞。确定与外周血水平、HPV状态、EGFR表达、临床肿瘤和患者特征及结局的相关性。患者接受单疗程新辅助化疗（顺铂，5-氟尿嘧啶），随后手术（无应答者）或放化疗（顺铂100 mg/m2，每3周× 3; 70戈伊，每日2戈伊× 7周）。中位随访时间为6.6年。HPV-16阳性患者的生存率提高（p=0.016）。T细胞浸润程度与HPV状态无差异，但与疾病特异性（DSS）和总生存期（OS）显著相关。CD 8、CD 4和FoxP 3亚群浸润程度越高，T分期越低，生存率越低。即使在调整HPV状态后，CD 8、FoxP 3和总T细胞与DSS（p=0.0236; 0.0040; 0.0197）和OS（分别为p=0.0137; 0.0158; 0.0115）显著相关。较少的T细胞浸润（p=0.0130）和特别是CD 4细胞（p=0.0792）与较高的EGFR表达相关。FoxP 3浸润与CD 4和CD 8浸润显著直接相关，但与外周血水平无关。改善的结局与独立于HPV状态的TIL增加相关，并表明对HPV-16的局部免疫应答可能部分与肿瘤大小、EGFR表达、吸烟史、体能状态或先天免疫等因素相关。由于核心样本量小和组织核心中肿瘤代表性的变化，组织微阵列中TIL的评估是困难的。进一步研究更多的患者和浸润在整个肿瘤切片结合功能分析的个别子集可能是必要的，以检测HPV-16相关癌症的局部免疫的差异。
Human Papillomavirus-16 (HPV-16) associated squamous carcinoma of the oropharynx has a favorable prognosis. Patients with HPV-16 positive cancers have elevated peripheral blood CD8+ T lymphocyte levels that correlate with response to chemotherapy and survival. Tumor infiltrating lymphocyte subpopulations (TIL) were assessed in pretreatment biopsies from a prospective patient cohort to determine if TIL subsets differed by HPV status, clinical factors, patient outcome or correlated with peripheral blood T cell levels. Measured were CD8, CD4, CD68 and Treg (FoxP3) lymphocytes by immunohistochemistry in a tissue microarray created from patients (n=46) with advanced oropharynx cancer. Correlations with peripheral blood levels, HPV status, expression of EGFR, clinical tumor and patient characteristics and outcome were determined. Patients were treated with a single course of neoadjuvant chemotherapy (cisplatin, 5-fluorouracil) followed by either surgery (non-responders) or chemoradiation (cisplatin 100 mg/m2 every 3 weeks × 3; 70 Gy, 2 Gy daily × 7 wks) for responders. Median follow up was 6.6 years. HPV-16 positive patients had improved survival (p=0.016). Degree of T cell infiltration did not differ by HPV status but was significantly related to disease specific (DSS) and overall survival (OS). Higher infiltration by CD8, CD4 and FoxP3 subsets was significantly associated with lower T stage and survival. Even after adjusting for HPV status, CD8, FoxP3 and total T cells were significantly associated with DSS (p=0.0236; 0.0040; 0.0197) and OS (p=0.0137; 0.0158; 0.0115, respectively). Less T cell infiltration (p=0.0130) and CD4 cells in particular (p=0.0792) were associated with higher EGFR expression. FoxP3 infiltration correlated significantly and directly with CD4 and CD8 infiltration but not with peripheral blood levels. Improved outcomes are associated with increased TILs independent of HPV status and suggest the local immune response to HPV-16 may be related in part to factors such as tumor size, EGFR expression, smoking history, performance status or innate immunity. Assessment of TILs in tissue microarrays is difficult due to small core sample size and variation in tumor representation in tissue cores. Further study of larger numbers of patients and infiltrates in whole tumor sections combined with functional analysis of individual subsets may be necessary to detect differences in local immunity in HPV-16 related cancers.
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影响因子：
11.5
作者：
Badoual, C;Hans, S;Tartour, E
通讯作者：
Tartour, E
影响因子：
45.3
作者：
Thurlow, Johanna K.;Murillo, Claudia L. Pena;Kalna, Gabriela
通讯作者：
Kalna, Gabriela
影响因子：
--
作者：
Wansom, Derrick;Light, Emily;Worden, Frank;Prince, Mark;Urba, Susan;Chepeha, Douglas B.;Cordell, Kitrina;Eisbruch, Avraham;Taylor, Jeremy;D'Silva, Nisha;Moyer, Jeffrey;Bradford, Carol R.;Kurnit, David;Kumar, Bhavna;Carey, Thomas E.;Wolf, Gregory T.
通讯作者：
Wolf, Gregory T.
影响因子：
11.5
作者：
Chung, Christine H.;Gillison, Maura L.
通讯作者：
Gillison, Maura L.
DOI：
10.1056/nejmoa0912217
发表时间：
2010-07-01
期刊：
The New England journal of medicine
影响因子：
--
作者：
Ang KK;Harris J;Wheeler R;Weber R;Rosenthal DI;Nguyen-Tân PF;Westra WH;Chung CH;Jordan RC;Lu C;Kim H;Axelrod R;Silverman CC;Redmond KP;Gillison ML
通讯作者：
Gillison ML