Cells. 2024;13(18):cells13181557.

Comparison of Tumor Microenvironments between Primary Tumors and Lymph Node Metastases in Head and Neck Squamous Cell Carcinoma and Their Predictive Role in Immune Checkpoint Inhibitor Treatment.

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제1저자 김동현 · 교신저자 김범석

PMID 39329741 PMC11429639 DOI 10.3390/cells13181557 IF 6 혈액종양내과

소속 (6)

Department of Internal Medicine, Seoul National University Hospital, Seoul 03080, Republic of Korea.
Department of Translational Medicine, Seoul National University College of Medicine, Seoul 03080, Republic of Korea.
Lunit Inc., Seoul 06241, Republic of Korea.
Department of Pathology, Seoul National University Hospital, Seoul 03080, Republic of Korea.
Cancer Research Institute, Seoul National University College of Medicine, Seoul 03080, Republic of Korea.
Department of Otorhinolaryngology-Head and Neck Surgery, Seoul National University Hospital, Seoul 03080, Republic of Korea.

Abstract

The relationship between tumor microenvironments (TMEs) of regional lymph node metastases (LNMs) and primary tumors in head and neck squamous cell carcinoma (HNSCC) remains unclear. This study compared tumor-infiltrating lymphocytes (TILs) and the immune phenotype (IP), characterized by spatial TIL distribution, between primary tumors and LNMs. Twenty-one HNSCC patients with regional LNM who received immune checkpoint inhibitors (ICIs) were included. A paired comparative analysis of TIL densities and IP between primary tumors and LNMs revealed no significant difference or correlation between TIL densities in primary tumors and LNMs. Their IPs were discordant in 12 patients (57.1%). Patients with high intratumoral TIL exhibited longer progression-free survival (PFS) than those with low intratumoral TIL in both primary tumors (median, 5.2 vs. 1.3 months, p = 0.003) and LNMs (median, 30.2 vs. 1.3 months, p = 0.012). Patients with inflamed IP exhibited longer PFS than those with non-inflamed IP in both primary tumors (median, 4.5 vs. 1.3 months, p = 0.043) and LNMs (median, 4.1 vs. 1.3 months, p = 0.037). Given the lack of correlation in TIL densities, the discrepancies in IP, and the predictive value of both TMEs, evaluating the TMEs of both primary tumors and LNMs may be beneficial for the precise use of ICIs in HNSCC. There was a significant discordance between the TME of primary tumors and LNMs, with implications in survival outcomes. Therefore, evaluating the TME of both the primary tumor and LNM could be beneficial for the precise use of ICIs in HNSCC.

Keywords

head and neck squamous cell carcinomaimmune phenotypelymph node metastasistumor microenvironmenttumor-infiltrating lymphocyte

Figures

**Figure 1** Sankey plot showing changes in the immune phenotype.

**Figure 2** Representative image of cancerous areas using Lunit SCOPE IO. Lunit SCOPE IO-inferenced images from four patients where the immune phenotypes of the primary tumor and lymph node metastasis are inflamed-inflamed, inflamed-desert, desert-inflamed, and desert-desert, respectively.

**Figure 3** Kaplan–Meier curves of progression-free survival based on tumor-infiltrating lymphocyte (TIL) density. (a) High intratumoral TIL (iTIL) vs. low iTIL in the primary tumor; (b) high stromal TIL (sTIL) vs. low sTIL in the primary tumor; (c) high iTIL vs. low iTIL in lymph node metastasis; (d) high sTIL vs. low sTIL in lymph node metastasis.

**Figure 4** Kaplan–Meier curves of progression-free survival based on immune phenotype (IP). (a) Inflamed vs. non-inflamed IP in lymph node metastasis. (b) Inflamed vs. non-inflamed IP in the primary tumor. (c) Desert vs. non-desert IP in lymph node metastasis. (d) Desert vs. non-desert IP in the primary tumor. (e) Non-desert IP in both the primary tumor and lymph node metastasis vs. desert IP in either site. (f) Desert vs. non-desert IP in lymph node metastasis in patients with a non-desert primary tumor.

그림 출처: PubMed Central 공개 논문 (PMC11429639)

Conflict of interest statement

BK 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. JSA, MK, GP, YL, and SH are employees of Lunit, while CYO holds a leadership position and is a stock owner of Lunit.

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