---
title: "CD39+CD103+CD8+ T cells (DP) improve neoadjuvant chemoimmunotherapy response in HNSCC"
id: "british-journal-of-cancer-0-cd39-cd103-cd8-t-cells-enhance-neoadjuvant-chemoimmunotherapy-efficacy-in-head"
canonical_url: "https://medichelpline.com/clinical-feed/british-journal-of-cancer-0-cd39-cd103-cd8-t-cells-enhance-neoadjuvant-chemoimmunotherapy-efficacy-in-head"
content_type: "clinical_feed_article"
specialty: "Oncology"
source_name: "British Journal of Cancer"
source_url: "https://www.nature.com/articles/s41416-026-03588-7"
published_at: "2026-08-20T05:00:16.000Z"
evidence_level: "Journal Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# CD39+CD103+CD8+ T cells (DP) improve neoadjuvant chemoimmunotherapy response in HNSCC
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/british-journal-of-cancer-0-cd39-cd103-cd8-t-cells-enhance-neoadjuvant-chemoimmunotherapy-efficacy-in-head
- **Specialty:** [Oncology](https://medichelpline.com/clinical-feed/oncology.md)
- **Primary Source:** British Journal of Cancer
- **Source URL:** [Original Journal Publication](https://www.nature.com/articles/s41416-026-03588-7)
- **Published At:** 2026-08-20T05:00:16.000Z
- **Evidence Rating:** Journal Feed
## Executive GIST (TL;DR)
- Neoadjuvant chemoimmunotherapy (NACI) improves outcomes in head and neck squamous cell carcinoma (**HNSCC**), but some patients show limited response due to insufficient anti-tumor T cells. - The study combined multicolor immunohistochemistry (mIHC) and single-cell RNA sequencing (scRNA-seq) to profile tumor-infiltrating T cells in NACI-treated HNSCC. - A distinct population of **CD39+CD103+ (double-positive, DP) CD8+ T cells** was markedly enriched in clinical responders to NACI. - mIHC confirmed that higher **DP CD8+ T cell density** correlated with NACI response in patient samples. - Functional assays and single-cell transcriptional profiling indicated DP CD8+ T cells display enhanced tumor-reactive **cytotoxic activity** compared with other CD8+ subsets. - Cell-cell interaction and spatial analyses identified a regulatory relationship between DP CD8+ T cells and a cancer-associated fibroblast subset defined as **CD90+CD138+ CAFs** (desmoplastic CAFs, dCAFs). - In vitro co-culture experiments suggested that **CD90+CD138+ CAF-derived LAMA4** may suppress the antitumor function of DP CD8+ T cells. - The authors propose that DP CD8+ T cells are critical mediators of NACI efficacy and that targeting **CD90+CD138+ CAFs** or their secreted factors (for example, **LAMA4**) could be a strategy to potentiate anti-tumor immunity. - Data supporting the study are available from the corresponding author upon reasonable request. - Figures in the source illustrate increased DP CD8+ T cell density with better prognosis, the cytotoxic phenotype of DP CD8+ T cells, crosstalk with CD90+CD138+ CAFs, a negative spatial correlation between DP CD8+ T cells and these CAFs, and a proposed LAMA4-mediated inhibitory mechanism.
## Clinical Analysis & Structured Key Points
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[nature](https://www.nature.com/) 2. [british journal of cancer](https://www.nature.com/bjc) 3. [articles](https://www.nature.com/bjc/articles?type=article) 4. article * Article * Published: 20 August 2026 Cellular and Molecular Biology # CD39+CD103+CD8+ T cells enhance neoadjuvant chemoimmunotherapy efficacy in head and neck squamous cell carcinoma * [Suling Chen](https://www.nature.com/articles/s41416-026-03588-7#auth-Suling-Chen-Aff1-Aff2) [ORCID: orcid.org/0009-0002-7104-0555](https://orcid.org/0009-0002-7104-0555)[1](https://www.nature.com/articles/s41416-026-03588-7#Aff1),[2](https://www.nature.com/articles/s41416-026-03588-7#Aff2) [na1](https://www.nature.com/articles/s41416-026-03588-7#na1), * [Yupeng Wu](https://www.nature.com/articles/s41416-026-03588-7#auth-Yupeng-Wu-Aff1-Aff2)[1](https://www.nature.com/articles/s41416-026-03588-7#Aff1),[2](https://www.nature.com/articles/s41416-026-03588-7#Aff2) [na1](https://www.nature.com/articles/s41416-026-03588-7#na1), * [Guangxin Rao](https://www.nature.com/articles/s41416-026-03588-7#auth-Guangxin-Rao-Aff1-Aff2)[1](https://www.nature.com/articles/s41416-026-03588-7#Aff1),[2](https://www.nature.com/articles/s41416-026-03588-7#Aff2) [na1](https://www.nature.com/articles/s41416-026-03588-7#na1), * [Weihao Tong](https://www.nature.com/articles/s41416-026-03588-7#auth-Weihao-Tong-Aff1-Aff2)[1](https://www.nature.com/articles/s41416-026-03588-7#Aff1),[2](https://www.nature.com/articles/s41416-026-03588-7#Aff2) [na1](https://www.nature.com/articles/s41416-026-03588-7#na1), * [Jingbin Huo](https://www.nature.com/articles/s41416-026-03588-7#auth-Jingbin-Huo-Aff1-Aff2)[1](https://www.nature.com/articles/s41416-026-03588-7#Aff1),[2](https://www.nature.com/articles/s41416-026-03588-7#Aff2) [na1](https://www.nature.com/articles/s41416-026-03588-7#na1), * [Guoxin Huang](https://www.nature.com/articles/s41416-026-03588-7#auth-Guoxin-Huang-Aff1-Aff2)[1](https://www.nature.com/articles/s41416-026-03588-7#Aff1),[2](https://www.nature.com/articles/s41416-026-03588-7#Aff2), * [Wenhao Sun](https://www.nature.com/articles/s41416-026-03588-7#auth-Wenhao-Sun-Aff1)[1](https://www.nature.com/articles/s41416-026-03588-7#Aff1), * [Songjiu Li](https://www.nature.com/articles/s41416-026-03588-7#auth-Songjiu-Li-Aff3)[3](https://www.nature.com/articles/s41416-026-03588-7#Aff3), * [Chenchang Li](https://www.nature.com/articles/s41416-026-03588-7#auth-Chenchang-Li-Aff2)[2](https://www.nature.com/articles/s41416-026-03588-7#Aff2), * [Shengguo Hu](https://www.nature.com/articles/s41416-026-03588-7#auth-Shengguo-Hu-Aff4)[4](https://www.nature.com/articles/s41416-026-03588-7#Aff4), * [Yingnan Ma](https://www.nature.com/articles/s41416-026-03588-7#auth-Yingnan-Ma-Aff1)[1](https://www.nature.com/articles/s41416-026-03588-7#Aff1), * [Ruiqi Zhu](https://www.nature.com/articles/s41416-026-03588-7#auth-Ruiqi-Zhu-Aff4)[4](https://www.nature.com/articles/s41416-026-03588-7#Aff4), * [Diya Wang](https://www.nature.com/articles/s41416-026-03588-7#auth-Diya-Wang-Aff1-Aff2)[1](https://www.nature.com/articles/s41416-026-03588-7#Aff1),[2](https://www.nature.com/articles/s41416-026-03588-7#Aff2), * [Meijuan Zhang](https://www.nature.com/articles/s41416-026-03588-7#auth-Meijuan-Zhang-Aff1)[1](https://www.nature.com/articles/s41416-026-03588-7#Aff1), * [Qi’an Chen](https://www.nature.com/articles/s41416-026-03588-7#auth-Qi_an-Chen-Aff5)[5](https://www.nature.com/articles/s41416-026-03588-7#Aff5), * [Xiao Tan](https://www.nature.com/articles/s41416-026-03588-7#auth-Xiao-Tan-Aff1) [ORCID: orcid.org/0009-0000-1449-1312](https://orcid.org/0009-0000-1449-1312)[1](https://www.nature.com/articles/s41416-026-03588-7#Aff1) [na2](https://www.nature.com/articles/s41416-026-03588-7#na2), * [Jinsong Li](https://www.nature.com/articles/s41416-026-03588-7#auth-Jinsong-Li-Aff1-Aff2) [ORCID: orcid.org/0000-0001-6833-5390](https://orcid.org/0000-0001-6833-5390)[1](https://www.nature.com/articles/s41416-026-03588-7#Aff1),[2](https://www.nature.com/articles/s41416-026-03588-7#Aff2) [na2](https://www.nature.com/articles/s41416-026-03588-7#na2), * [Zhaoyu Lin](https://www.nature.com/articles/s41416-026-03588-7#auth-Zhaoyu-Lin-Aff1-Aff2) [ORCID: orcid.org/0009-0006-5897-108X](https://orcid.org/0009-0006-5897-108X)[1](https://www.nature.com/articles/s41416-026-03588-7#Aff1),[2](https://www.nature.com/articles/s41416-026-03588-7#Aff2) [na2](https://www.nature.com/articles/s41416-026-03588-7#na2) & * … * [Bowen Li](https://www.nature.com/articles/s41416-026-03588-7#auth-Bowen-Li-Aff1-Aff2) [ORCID: orcid.org/0000-0003-0148-5030](https://orcid.org/0000-0003-0148-5030)[1](https://www.nature.com/articles/s41416-026-03588-7#Aff1),[2](https://www.nature.com/articles/s41416-026-03588-7#Aff2) [na2](https://www.nature.com/articles/s41416-026-03588-7#na2) Show authors [_British Journal of Cancer_](https://www.nature.com/bjc) (2026) [Cite this article](https://www.nature.com/articles/s41416-026-03588-7#citeas) [ Save article ](https://www.nature.com/articles/s41416-026-03588-7/save-research?_csrf=VVy9g8CeZlJnU1o-E4_9cKP_QlSY24fD) [ View saved research ](https://www.nature.com/saved-research) ## Abstract ### Background Neoadjuvant chemoimmunotherapy (NACI) has revolutionized head and neck squamous cell carcinoma (HNSCC) treatment. However, some patients still do not respond significantly, partly attributed to insufficient anti-tumor specific T-cells. Thus, identifying the underlying causes of impaired antitumor immunity has become an urgent priority to improve efficacy. ### Methods To investigate the link between anti-tumor specific T cells and NACI efficacy in treating HNSCC, we employed multicolor immunohistochemistry (mIHC) and single-cell RNA sequencing (scRNA-seq). To gain deeper insights into the regulatory mechanisms of these T cell populations, we performed cell-cell interaction analysis and spatial analysis. Furthermore, co-culture experiments were carried out to explore the interactions between the cells. ### Results Our scRNA-seq results indicated that the population of CD39+CD103+ (double-positive, DP) CD8+ T cells was dramatically increased in the responders of NACI-treated HNSCC patients, while mIHC analysis confirmed the correlation between DP CD8+ T cells density and NACI response. Functional assays demonstrated that DP CD8+ T cells constitute a distinct T cell subset exhibiting enhanced cytotoxic activity. The cell-cell interaction analysis revealed that DP CD8+ T cells were regulated by the CD90+CD138+ cancer-associated fibroblasts (CAFs) subset, which has been characterized as desmoplastic CAFs (dCAFs). In vitro mechanistic experiments suggested that CD90+CD138+ CAF-derived LAMA-4 may reduce the antitumor capacity of DP CD8+ T cells. ### Conclusions Our study highlights the critical role of DP CD8+ T cells in enhancing NACI efficacy. Meanwhile, further research is warranted to explore the effects of targeting CD90+CD138+ CAFs,a thus regulating the function of DP CD8+ T cells. This is a preview of subscription content, [access via your institution](https://wayf.springernature.com?redirect_uri=https%3A%2F%2Fwww.nature.com%2Farticles%2Fs41416-026-03588-7) ## Access options [ Access through your institution ](https://wayf.springernature.com?redirect_uri=https%3A%2F%2Fwww.nature.com%2Farticles%2Fs41416-026-03588-7) Subscribe to this journal Receive 24 print issues and online access 251,40 € per year only 10,48 € per issue [Learn more](https://www.nature.com/bjc/subscribe) Buy this article * Purchase on SpringerLink * Instant access to the full article PDF. 39,95 € Prices may be subject to local taxes which are calculated during checkout ### Additional access options: * [Log in](https://idp.nature.com/authorize/natureuser?client_id=grover&redirect_uri=https%3A%2F%2Fwww.nature.com%2Farticles%2Fs41416-026-03588-7) * [Learn about institutional subscriptions](https://www.springernature.com/gp/librarians/licensing/license-options) * [Read our FAQs](https://support.nature.com/en/support/home) * [Contact customer support](https://www.springernature.com/gp/contact) **Fig. 1: An increased density of DP CD8 + T cells is associated with a better prognosis in HNSCC patients receiving NACI treatment.** ![](https://media.springernature.com/m312/springer-static/image/art%3A10.1038%2Fs41416-026-03588-7/MediaObjects/41416_2026_3588_Fig1_HTML.png) **Fig. 2: DP CD8 + T cells exhibit tumor-reactive cytotoxic function.** ![](https://media.springernature.com/m312/springer-static/image/art%3A10.1038%2Fs41416-026-03588-7/MediaObjects/41416_2026_3588_Fig2_HTML.png) **Fig. 3: Crosstalk between DP CD8 + T cells and CD90+CD138+ CAFs.** ![](https://media.springernature.com/m312/springer-static/image/art%3A10.1038%2Fs41416-026-03588-7/MediaObjects/41416_2026_3588_Fig3_HTML.png) **Fig. 4: Negative correlation between DP CD8 + T cell and CD90+CD138+ CAFs.** ![](https://media.springernature.com/m312/springer-static/image/art%3A10.1038%2Fs41416-026-03588-7/MediaObjects/41416_2026_3588_Fig4_HTML.png) **Fig. 5: CD138 +CD90+ CAFs may exert a negative regulatory effect on the function of DP CD8+ T cell through LAMA4 secretion.** ![](https://media.springernature.com/m312/springer-static/image/art%3A10.1038%2Fs41416-026-03588-7/MediaObjects/41416_2026_3588_Fig5_HTML.png) ### Similar content being viewed by others ![](https://media.springernature.com/w215h120/springer-static/image/art%3A10.1038%2Fs41467-025-63696-5/MediaObjects/41467_2025_63696_Fig1_HTML.png) ### [Tumor immune dynamics and long-term clinical outcome of stage IIIA NSCLC patients treated with neoadjuvant chemoimmunotherapy ](https://www.nature.com/articles/s41467-025-63696-5?fromPaywallRec=true) Article Open access 30 September 2025 ![](https://media.springernature.com/w215h120/springer-static/image/art%3A10.1038%2Fs41435-025-00330-w/MediaObjects/41435_2025_330_Fig1_HTML.png) ### [Characterizing the immune landscape of tumor-infiltrating lymphocytes in non-small cell lung cancer ](https://www.nature.com/articles/s41435-025-00330-w?fromPaywallRec=true) Article 05 May 2025 ![](https://media.springernature.com/w215h120/springer-static/image/art%3A10.1038%2Fs41467-026-68676-x/MediaObjects/41467_2026_68676_Fig1_HTML.png) ### [ZNF683+ NK cells govern chemotherapy sensitivity in advanced HPSCC via reshaping immune microenvironment ](https://www.nature.com/articles/s41467-026-68676-x?fromPaywallRec=true) Article Open access 21 January 2026 ## Data availability The data that support the findings of this study are available from the corresponding author upon reasonable request. ## References 1. 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