帕博利珠单抗联合二甲双胍治疗转移性头颈部癌的 II 期可行性研究
A Phase II Feasibility Study Combining Pembrolizumab and Metformin in Patients with Metastatic Head and Neck Cancer.
二甲双胍联合帕博利珠单抗耐受性良好，仅出现轻度胃肠道不良事件，并展现出有前景的活性，值得在随机试验中进一步研究。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
感觉神经释放的 CGRP 通过抑制 TILs 促进 HNSCC 肿瘤生长
英文原题：Sensory nerve release of CGRP increases tumor growth in HNSCC by suppressing TILs.
查看英文原题
Sensory nerve release of CGRP increases tumor growth in HNSCC by suppressing TILs.
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研究概要
我们的数据支持感觉神经通过直接作用于适应性免疫系统，减少 TME 中的 Th1 CD4 T 细胞和活化 CD8 T 细胞，从而在加速肿瘤生长中发挥作用。这些数据支持进一步研究感觉神经在 HNSCC 的 TME 中的作用，并指向阻断感觉神经功能或特异性抑制 TME 内 CGRP 释放或活性以改善预后的可能治疗疗效。
研究思路结论见上方概要
背景
神经周围侵犯（PNI）和肿瘤微环境（TME）内的神经密度长期以来一直与头颈部鳞状细胞癌（HNSCC）的不良预后相关。这促使人们研究肿瘤微环境内的神经如何影响适应性免疫系统和肿瘤生长。
方法
我们使用来自近期一项 HNSCC 临床试验的人类肿瘤组织的 RNA 测序分析、HNSCC 患者人类神经的蛋白质组学，以及 HPV 无关型 HNSCC 的同源原位小鼠模型，来研究感觉神经如何调节适应性免疫系统。
结果
降钙素基因相关肽（CGRP）在体外直接抑制CD8 T细胞活性，而通过手术、药物或基因手段阻断感觉神经功能可在体内增强CD8和CD4 T细胞活性。
展开英文摘要原文
BACKGROUND
Perineural invasion (PNI) and nerve density within the tumor microenvironment (TME) have long been associated with worse outcomes in head and neck squamous cell carcinoma (HNSCC). This prompted an investigation into how nerves within the tumor microenvironment affect the adaptive immune system and tumor growth.
METHODS
We used RNA sequencing analysis of human tumor tissue from a recent HNSCC clinical trial, proteomics of human nerves from HNSCC patients, and syngeneic orthotopic murine models of HPV-unrelated HNSCC to investigate how sensory nerves modulate the adaptive immune system.
FINDINGS
Calcitonin gene-related peptide (CGRP) directly inhibited CD8 T cell activity in vitro, and blocking sensory nerve function surgically, pharmacologically, or genetically increased CD8 and CD4 T cell activity in vivo.
CONCLUSIONS
Our data support sensory nerves playing a role in accelerating tumor growth by directly acting on the adaptive immune system to decrease Th1 CD4 T cells and activated CD8 T cells in the TME. These data support further investigation into the role of sensory nerves in the TME of HNSCC and points toward the possible treatment efficacy of blocking sensory nerve function or specifically inhibiting CGRP release or activity within the TME to improve outcomes. FUNDING: 1R01DE028282-01, 1R01DE028529-01, 1P50CA261605-01 (to S.D.K.), 1R01CA284651-01 (to S.D.K.), and F31 DE029997 (to L.B.D.).
论文信息
- 作者
- Darragh LB、Nguyen A、Pham TT、Idlett-Ali S、Knitz MW、Gadwa J、Bukkapatnam S、Corbo S
- 第一作者单位
- Department of Radiation Oncology, University of Colorado Denver at Anschutz Medical Campus, Aurora, CO, USA; Department of Immunology and Microbiology, University of Colorado Denver at Anschutz Medical Campus, Aurora, CO, USA.United States
- 通讯作者单位
- Department of Radiation Oncology, University of Colorado Denver at Anschutz Medical Campus, Aurora, CO, USA; Department of Immunology and Microbiology, University of Colorado Denver at Anschutz Medical Campus, Aurora, CO, USA. Electronic address: sana.karam@cuanschutz.edu.United States
- 文献类型
- 非美国政府资助研究 · 美国 NIH 院内研究
- 期刊
- Med (New York, N.Y.)2024 Mar 8
- 原文标识
- PubMed 38423011 · DOI 10.1016/j.medj.2024.02.002
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