PO.ET02.11 · 实验与分子治疗

针对头颈部鳞状细胞癌前哨淋巴结的结内趋化因子治疗

Intranodal chemokine therapy targeting the sentinel lymph node in head and neck squamous cell carcinoma

编号 448 展板 18 时间 4/19 02:00–05:00 区域 Section 18 主讲 Anais Zourelidis, MD

分会场 Novel Therapeutics and Drug Targets 1

查看 PDF 下载 PDF 🔒 查看 / 下载完整 PDF 需登录并开通下载套餐 · 查看套餐 / 开通 AACR 官方页面

作者与单位 Authors & Affiliations

Anais Aurelia Zourelidis¹, Jonathan Gunn², Tomoya Kurokawa¹, Sayuri Miyauchi¹, Kelsey Decker¹, Peter Vo¹, Pardis Mohammadzadeh¹, Jason Wu², Ester J. Kwon², Joseph A. Califano¹

¹Moores Cancer Center, University of California San Diego, La Jolla, CA,²Shu Chien-Gene Lay Department of Bioengineering, University of California San Diego, La Jolla, CA

摘要 Abstract

中文摘要

新出现的证据凸显了淋巴保留策略在头颈部鳞状细胞癌(HNSCC)中的潜力，以及前哨淋巴结(SLN)作为关键免疫学生态位的作用1-3。在此背景下，CCR7⁺树突状细胞(DCs)已被确认为免疫放疗应答的一个重要亚群4。在此，我们研究了使用缓释纤维蛋白凝胶偶联系统将结内CCR7激动剂CCL19/21递送至SLN的治疗效果，采用同基因、原位、部分对程序性死亡-1抑制剂(PD-1i)敏感的4MOSC1 HNSCC模型5，旨在增强肿瘤-SLN轴上的DC功能。将4MOSC1细胞注射入C57Bl/6小鼠的颊间隙，并进行SLN定位标测，然后在肿瘤植入6天后分别注射：与纤维蛋白原偶联(con.)的结内(i.n.)CCL19/21、未与纤维蛋白原偶联(uncon.)的i.n. CCL19/21、腹腔内(i.p.)PD-1i、与纤维蛋白原偶联的i.n. CCL19/21 + i.p. PD-1i，或假手术。监测动物的肿瘤体积和生存情况。用流式细胞术检测原发肿瘤。结内偶联CCL19/21导致肿瘤生长显著减少(p=<0.0001 vs.假手术)，完全缓解(CR)率为60%，而未偶联i.n. CCL19/21(p=0.3354 vs.假手术)和假手术组则无CR。偶联CCL19/21 + PD-1i的联合治疗显著改善了总生存，第34天时生存率为80%，而i.n.偶联CCL19/21为60%，未偶联i.n. CCL19/21和对照组为0%。治疗48小时后的流式细胞分析显示，偶联CCL19/21治疗的小鼠肿瘤中DCs增多且活化DCs增强。结内递送CCR7激动剂CCL19/21显著增强肿瘤中的DCs和活化DCs，减少肿瘤生长，并延长HNSCC 4MOSC1小鼠模型的生存。 1. Delclaux I等 2024;10(1):28-37。2. Saddawi-Konefka R等 2022;13(1):4298。3. Cochran AJ等 2006;6(9):659-670。4. Saddawi-Konefka R等 2025;16(1):6578。5. Wang Z等 2019;10(1):5546。

查看英文原文 English abstract

Emerging evidence highlights the potential of lymphatic-sparing strategies in head and neck squamous cell carcinoma (HNSCC), as well as the sentinel lymph node (SLN) as a critical immunological niche 1-3 . Within this context, CCR7⁺ dendritic cells (DCs) have been identified as an essential subpopulation for the response to immunoradiotherapy 4 . Here, we investigated the therapeutic effect of intranodal CCR7 agonists CCL19/21 into the SLN using a sustained-release fibrin gel-conjugate system in the syngeneic, orthotopic, partially programmed death-1 inhibitor (PD-1i) sensitive 4MOSC1 model of HNSCC 5 , aiming to enhance DC function along the tumor-SLN axis. C57Bl/6 mice were injected with 4MOSC1 cells in the buccal space and underwent SLN mapping and injection of CCL19/21 conjugated (con.) to fibrinogen intranodal (i.n.), CCL19/21 unconjugated (uncon.) to fibrinogen i.n., PD-1i intraperitoneal (i.p.), CCL19/21 con. to fibrinogen i.n. + PD-1i i.p., or sham surgery following 6 days after tumor implantation. Animals were monitored for tumor volume and survival. Primary tumors were assayed by flow cytometry. Intranodal con. CCL19/21 led to a significantly reduced tumor growth (p= <0,0001 vs. sham) and complete response (CR) rate of 60%, whereas uncon. CCL19/21 i.n. (p=0,3354 vs. sham) and sham groups showed no CR. Combination of con. CCL19/21 + PD-1i significantly improved overall survival with 80% survival by day 34, compared to 60% for con. CCL19/21 i.n., and 0% for uncon. CCL19/21 i.n. and controls. Flow cytometric analysis 48 h following treatment shows enhanced DCs and enhanced activated DCs in tumors in con. CCL19/21 treated mice. Intranodal delivery of CCR7 agonists CCL19/21 significantly enhances DCs and activated DCs in tumors, reduces tumor growth and prolongs survival in the HNSCC 4MOSC1 mouse model. 1. Delclaux I et al. 2024;10(1):28-37.2. Saddawi-Konefka R et al. 2022;13(1):4298.3. Cochran AJ et al. 2006;6(9):659-670.4. Saddawi-Konefka R et al. 2025;16(1):6578.5. Wang Z et al. 2019;10(1):5546.

利益披露 Disclosure

A. A. Zourelidis, None.. J. Gunn, None.. T. Kurokawa, None.. S. Miyauchi, None.. K. Decker, None.. P. Vo, None.. P. Mohammadzadeh, None.. J. Wu, None.. E. J. Kwon, None.. J. A. Califano, None.

← 返回 AACR 2026 检索