ArticleCancer immunology, immunotherapy : CII2025
Tumor-draining lymph nodes respond to immune checkpoint inhibition and orchestrate tumor immune remodeling.
Article in Cancer immunology, immunotherapy : CII, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- A Phase II Study of Stereotactic Ablative Radiotherapy plus Atezolizumab plus Tiragolumab in Treatment-Naïve Patients with Advanced Non-Small Cell Lung Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Trial
- Follicular T cells in the ovarian cancer immune microenvironment: biological insights and translational implications.Frontiers in immunology · 2026Review
- The tumor immune microenvironment of thyroid cancer and colorectal cancer: cellular crosstalk and therapeutic implications.Frontiers in immunology · 2026Review
- Mechanistic mathematical modeling of abscopal effect reveals mechanisms of off-target tumor response.Frontiers in immunology · 2026Article
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Authors and funding
14 authors.
Funding
Abstract
backgroundImmune checkpoint inhibitors have traditionally been understood to exert their effects primarily within the tumor microenvironment, particularly targeting CD8 + T cells. However, recent studies have highlighted a pivotal role of tumor-draining lymph nodes in mediating responses to immune checkpoint inhibitor therapy. This study aimed to elucidate the specific mechanisms by which tumor-draining lymph nodes respond to immune checkpoint inhibitor therapy and regulate the tumor microenvironment in human colorectal cancer.
methodsWe performed single-cell RNA sequencing and T cell receptor sequencing on tumor-draining lymph nodes and tumor tissues from patients with colorectal cancer. Through in-depth analysis of the single-cell data, we established the connection between TDLNs and tumor, and explored the impact of immune checkpoint inhibitor therapy on the immune microenvironment of tumor-draining lymph nodes. In addition, we conducted animal experiments to validate these findings.
resultsOur findings revealed that immune checkpoint inhibitor treatment induced the expansion of tumor-specific CD8 + effector memory T cells within tumor-draining lymph nodes, which may serve as a source for the progenitor-exhausted CD8 + T cells in the tumor microenvironment. Moreover, conventional dendritic cells type 1 and macrophages within tumor-draining lymph nodes facilitated this process. We also observed that immune checkpoint inhibitor therapy promoted the expansion of tumor-specific CD4 + follicular helper T cells in tumor-draining lymph nodes, which may explain the increase of CD4 + follicular helper T cells in the tumor microenvironment after immune checkpoint inhibitor therapy. These hypotheses were corroborated through experiments in mice.
conclusionsOur findings delineate the critical regulatory function of tumor-draining lymph nodes in modulating the tumor microenvironment during Immune checkpoint inhibitor therapy.
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