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. 2024 Nov 20;15(1):686.
doi: 10.1007/s12672-024-01504-0.

Changes in the tumor microenvironment in recurrent head and neck squamous cell carcinoma and its implication on efficacy of immune checkpoint inhibitors

Dong Hyun Kim  1   2 , Mingu Kang  3 , Gahee Park  3 , Mohammad Mostafavi  3 , Yoojoo Lim  3 , Chan-Young Ock  3 , Jiwon Koh  4   5 , Yoon Kyung Jeon  4   5 , Kyeong Cheon Jung  4 , Soon-Hyun Ahn  6 , Eun-Jae Chung  6 , Seong-Keun Kwon  6 , Bhumsuk Keam  7   8
Affiliations

Changes in the tumor microenvironment in recurrent head and neck squamous cell carcinoma and its implication on efficacy of immune checkpoint inhibitors

Dong Hyun Kim et al. Discov Oncol. .

Abstract

Little is known about changes in the abundance of tumor-infiltrating lymphocytes (TILs) and immune phenotype (IP) in recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). We aimed to compare the TILs and IP between initial and recurrent HNSCCs using paired analysis. Thirty-seven patients who experienced recurrence after surgical resection and received treatment with immune checkpoint inhibitors (ICIs) between June 2014 and June 2023 were included. Changes in intratumoral TIL (iTILs), stromal TIL (sTILs), and IPs were subjected to paired analysis between the initial and recurrent tumors. We investigated their relationship with the outcomes of ICIs. The density of iTIL and sTIL in the recurrent tumors was significantly lower compared to initial tumors. IP was significantly different; the proportion of desert IP was higher in recurrent tumors (83.8% vs. 35.1%, P < 0.001). Increased sTIL was a favorable indicator for overall response to ICIs and progression-free survival. Our findings suggest TILs decrease during recurrence compared with the initial tumor, resulting in a transition toward desert IP. Therefore, careful evaluation of TIL density in both initial and recurrent tumors is recommended when using ICIs in patients with R/M HNSCC.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: This study was conducted in accordance with the Declaration of Helsinki and Good Clinical Practice guidelines. The study protocol was approved by the Institutional Review Board of the Seoul National University Hospital (approval no. H-2306-142-1440). The requirement for informed consent was waived by the Institutional Review Board because of the study’s retrospective nature. Competing interests: B.K. received research funding from MSD, AstraZeneca, and Ono Pharmaceutical Co., Ltd., and has served as an advisor for Handok, NeoImmuneTec, Trialinformatics and ImmuneOncia outside of the current work. M.K., G.P., and Y.L. are employees of Lunit, and CY.O. holds a leadership position and is a stock owner of Lunit.

Figures

Fig. 1
Fig. 1
Changes in tumor microenvironment between the primary and recurrent tumor. A Changes in the density of intratumoral tumor-infiltrating lymphocyte; B Changes in the density of stromal tumor-infiltrating lymphocyte; C Changes in the inflamed score; D Changes in the immune-exclude score; E Changes in the immune-desert score
Fig. 2
Fig. 2
Flow chart (Sankey plot) showing changes in the immune phenotype
Fig. 3
Fig. 3
Survival outcomes based on changes in stromal tumor-infiltrating lymphocytes (TIL) density. A Progression-free survival; B Overall survival
Fig. 4
Fig. 4
Progression-free survival (PFS) based on the tumor microenvironment of recurrent tumor. A PFS based on the immune phenotype (desert vs. non-desert); B PFS based on the immune-desert score
See this image and copyright information in PMC

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