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Cited by 455Cancer Immunotherapy and BiomarkersT-cell and B-cell ImmunologyImmunotherapy and Immune Responses

Dynamic CD8+ T cell responses to cancer immunotherapy in human regional lymph nodes are disrupted in metastatic lymph nodes

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Rahim, Maha K., Okholm, Trine Line H., Jones, Kyle B., McCarthy, Elizabeth E., Liu, Candace C., Yee, Jacqueline L., Tamaki, Stanley J., Marquez, Diana M. +15 more·2023·Cell
DOI 10.1016/j.cell.2023.02.021PMC PMC10348701
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Abstract

CD8 + T cell responses are critical for anti-tumor immunity. While extensively profiled in the tumor microenvironment, recent studies in mice identified responses in lymph nodes (LNs) as essential; however, the role of LNs in human cancer patients remains unknown. We examined CD8 + T cells in human head and neck squamous cell carcinomas, regional LNs, and blood using mass cytometry, single-cell genomics, and multiplexed ion beam imaging. We identified progenitor exhausted CD8 + T cells (Tpex) that were abundant in uninvolved LN and clonally related to terminally exhausted cells in the tumor. After anti-PD-L1 immunotherapy, Tpex in uninvolved LNs reduced in frequency but localized near dendritic cells and proliferating intermediate-exhausted CD8 + T cells (Tex-int), consistent with activation and differentiation. LN responses coincided with increased circulating Tex-int. In metastatic LNs, these response hallmarks were impaired, with immunosuppressive cellular niches. Our results identify important roles for LNs in anti-tumor immune responses in humans.

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  • Single-cell sequencing has identified CD8+ T cell subsets with variable exhaustion levels in cancers, including terminal exhausted T (tTex) cells, TCF7+ progenitor exhausted T (Tpex) cells, GZMK+ effector/effector memory T (Teff/Tem) cells, and CXCL13+ Tpex cells.

    “Singe-cell sequencing has identified CD8+ T cell subsets with variable exhaustion levels in cancers, including terminal exhausted T (tTex) cells, TCF7+ progenitor exhausted T (Tpex) cells,”

    From Contrasting cytotoxic and regulatory T cell responses underlying distinct clinical outcomes to anti-PD-1 plus lenvatinib therapy in cancer (2025) · cites this paper as [22]

    Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

    Experimental — accuracy not yet measured

  • CD8+ T cells, primary targets for PD-1 blockade, show favorable responses across cancer types, including local clonal expansion and recruitment of circulating T cells.

    “CD8+ T cells, primary targets for PD-1 blockade, show favorable responses across cancer types, including local clonal expansion and recruitment of circulating T cells.”

    From Contrasting cytotoxic and regulatory T cell responses underlying distinct clinical outcomes to anti-PD-1 plus lenvatinib therapy in cancer (2025) · cites this paper as [22]

    The Introduction (page unavailable) describes CD8+ T cells as central to checkpoint-blockade efficacy and reports that new clones appear in tumors after treatment, supporting recruitment from the periphery. The Results section on clonally related T cells finds shared clones in lymph nodes and tumors, but does not establish local clonal expansion. This study examines head and neck cancer with anti-PD-L1 treatment, not favorable responses across cancer types to PD-1 blockade. (LLM, conf=0.86)

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Sorted by citations

Authors
Rahim, M. K., Okholm, T. L. H., Jones, K. B., McCarthy, E. E., Liu, C. C., Yee, J. L., Tamaki, S. J., Marquez, D. M., Tenvooren, I., Wai, K., Cheung, A., Davidson, B. R., Johri, V., Samad, B., O’Gorman, W. E., Krummel, M. F., van Zante, A., Combes, A. J., Angelo, M., Fong, L., Algazi, A. P., Ha, P., & Spitzer, M. H.
Affiliations
  • University of California, San Francisco (US)
  • Stanford University (US)
  • Genentech (US)
Corresponding author
Spitzer, Matthew H.
ORCID
Venue
Cell
Publisher
Elsevier BV
Published
2023-03
Volume
186
Issue
6
Pages
1127-1143.e18
ISSN
0092-8674 (ISSN-L)
DOI
10.1016/j.cell.2023.02.021
PMC
PMC10348701
OpenAlex
W4327575929
Cited by
455
References
13
Citations by year
2026: 120 · 2025: 152 · 2024: 132 · 2023: 51
FWCI
56.60
Type
journal article
Language
en
Open access
Licence
Locations
  • Cell (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • eScholarship (California Digital Library) (submittedVersion, cc-by)
Funders
  • Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco (S10 OD025187, S10 OD018040)
  • Carlsberg Foundation (CF19-0493)
  • University of California San Francisco
  • National Institutes of Health (S10 OD025187, S10 OD018040, R01 DE032033, DP5 OD023056)
  • Genentech Inc
  • National Science Foundation
  • Cancer Research Institute
  • Roche
  • National Institute of Dental and Craniofacial Research (K23DE029239)
Topics
  • Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
  • Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
Keywords
CD8+ T cells, regional lymph nodes, metastatic lymph nodes, PD-L1 blockade, T cell exhaustion, head and neck squamous cell carcinoma, dendritic cells, tumor microenvironment, antitumor immunity, immunosuppressive niche, T cell differentiation
MeSH terms
Animals, Humans, Immunotherapy, Lymph Nodes, Neoplasms, CD8-Positive T-Lymphocytes, Mice, Tumor Microenvironment

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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