Immune profiles in primary squamous cell carcinoma of the head and neck.
Immune profiles in primary squamous cell carcinoma of the head and neck.
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DOI：
10.1016/j.oraloncology.2019.06.032
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发表时间：
2019-09
期刊：
影响因子：
4.8
通讯作者：
Seiwert TY
中科院分区：
文献类型：
--
作者：
Saloura V;Izumchenko E;Zuo Z;Bao R;Korzinkin M;Ozerov I;Zhavoronkov A;Sidransky D;Bedi A;Hoque MO;Koeppen H;Keck MK;Khattri A;London N;Kotlov N;Fatima A;Vougiouklakis T;Nakamura Y;Lingen M;Agrawal N;Savage PA;Kron S;Kline J;Kowanetz M;Seiwert TY
In this study we describe the tumor microenvironment, the signaling pathways and genetic alterations associated with the presence or absence of CD8+ T-cell infiltration in primary squamous cell carcinoma of the head and neck (SCCHN) tumors. Two SCCHN multi-analyte cohorts were utilized, the Cancer Genome Atlas (TCGA) and the Chicago Head and Neck Genomics (CHGC) cohort. A well-established chemokine signature classified SCCHN tumors into high and low CD8+ T-cell inflamed phenotypes (TCIP-H, TCIP-L respectively). Gene set enrichment and iPANDA analyses were conducted to dissect differences in signaling pathways, somatic mutations and copy number aberrations for TCIP-H versus TCIP-L tumors, stratified by HPV status. TCIP-H SCCHN tumors were enriched in multiple immune checkpoints irrespective of HPV-status. HPV-positive tumors were enriched in markers of T-regulatory cells (Tregs) and HPV-negative tumors in protumorigenic M2 macrophages. TCIP-L SCCHN tumors were enriched for the β-catenin/WNT and Hedgehog signaling pathways, had frequent mutations in NSD1 and amplifications in EGFR, NSD3 and FGFR1. TCIP-H SCCHN tumors were associated with the MAPK/ERK, JAK/STAT and mTOR/AKT signaling pathways, and were enriched in CASP8, EP300, HRAS mutations, and CD274, PDCD1LG2 and JAK2 amplifications. Our findings support that combinatorial immune checkpoint blockade and depletion strategies targeting Tregs in HPV-positive and M2 macrophages in HPV-negative tumors may lead to improved antitumor immune responses in patients with TCIP-H SCCHN. We highlight novel pathways and genetic events that may serve as candidate biomarkers and novel targeted therapies to enhance the efficacy of immunotherapy in SCCHN patients.
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影响因子：
11.2
作者：
Harlin H;Meng Y;Peterson AC;Zha Y;Tretiakova M;Slingluff C;McKee M;Gajewski TF
通讯作者：
Gajewski TF
TIM-3 表达是肿瘤组织中调节性 T 细胞的特征，并与肺癌进展相关
影响因子：
3.7
作者：
Gao X;Zhu Y;Li G;Huang H;Zhang G;Wang F;Sun J;Yang Q;Zhang X;Lu B
通讯作者：
Lu B
DOI：
10.4137/bcbcr.s40182
发表时间：
2016
期刊：
Breast cancer : basic and clinical research
影响因子：
--
作者：
Garcia J;Lizcano F
通讯作者：
Lizcano F
影响因子：
4.8
作者：
Konsavage, Wesley M., Jr.;Kyler, Sydney L.;Yochum, Gregory S.
通讯作者：
Yochum, Gregory S.
影响因子：
6.6
作者：
Li C;Egloff AM;Sen M;Grandis JR;Johnson DE
通讯作者：
Johnson DE