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Cited by 86Cancer Immunotherapy and BiomarkersT-cell and B-cell ImmunologyImmunotherapy and Immune Responses

Progressive upregulation of PD-1 in primary and metastatic melanomas associated with blunted TCR signaling in infiltrating T lymphocytes

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Chapon, Maxime, Randriamampita, Clotilde, Maubec, Eve, Badoual, Cécile, Fouquet, Stéphane, Wang, Shu-Fang, Marinho, Eduardo, Farhi, David +9 more·2011·Journal of Investigative Dermatology
DOI 10.1038/jid.2011.30
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Abstract

Programmed death-1 (PD-1) is involved in T-cell tolerance to self-antigens. For some cancers, it has been suggested that the expression of a ligand of PD-1, namely PD-L1, could contribute to tumor escape from immune destruction. Nevertheless, the relationship between PD-1 expression on tumor-infiltrating T lymphocytes (TILs), disease stage, and TIL responsiveness is still poorly documented. In this study, we show that freshly isolated CD4(+) and CD8(+) TILs express substantial levels of PD-1 in primary melanomas. The expression of PD-1 was further increased at later stages in distant cutaneous metastases, especially on CD8(+) TILs. The expression of PD-1 ligands was frequent only in metastases, on both tumor cells and tumor-derived myeloid cells. TILs isolated from these cutaneous tumors are poorly reactive ex vivo, with blunted calcium response and IFN-γ production after TCR stimulation. Surprisingly, in distinct parts of a primary melanoma, either invasive or regressing, we show that TILs similarly express PD-1 and remain dysfunctional. The expressions of PD-1 and PD-L1 in metastatic melanoma lesions could be considered as witnesses of an unsuccessful anti-tumoral immune response, but the direct involvement of PD-1 in the severity of the disease, and the importance of TILs in tumor regression, remain to be established.

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Crossref · 10.1038/jid.2011.30

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  • PD-L1 on tumor cells or other infiltrating immune cells can disable PD-1-expressing tumor-infiltrating T cells.

    “PD-1-expressing tumor-infiltrating T cells can be disabled by PD-L1 on the surfaces of tumor cells or other infiltrating immune cells, and blocking antibodies targeting PD-1 signaling are therefore thought to mainly affect the effector stage of the immune response (13, 55–57).”

    From Anti-PD-1 and Anti-CTLA-4 Therapies in Cancer: Mechanisms of Action, Efficacy, and Limitations (2018) · cites this paper as [56]

  • Blocking antibodies targeting PD-1 signaling mainly affect the effector stage of the immune response.

    “PD-1-expressing tumor-infiltrating T cells can be disabled by PD-L1 on the surfaces of tumor cells or other infiltrating immune cells, and blocking antibodies targeting PD-1 signaling are therefore thought to mainly affect the effector stage of the immune response (13, 55–57).”

    From Anti-PD-1 and Anti-CTLA-4 Therapies in Cancer: Mechanisms of Action, Efficacy, and Limitations (2018) · cites this paper as [56]

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Authors
Chapon, M., Randriamampita, C., Maubec, E., Badoual, C., Fouquet, S., Wang, S.-F., Marinho, E., Farhi, D., Garcette, M., Jacobelli, S., Rouquette, A., Carlotti, A., Girod, A., Prévost-Blondel, A., Trautmann, A., Avril, M.-F., & Bercovici, N.
Affiliations
  • Centre National de la Recherche Scientifique (FR)
  • Assistance Publique – Hôpitaux de Paris (FR)
  • Inserm (FR)
  • Hôpital Cochin (FR)
  • Institut Curie (FR)
Corresponding author
Bercovici, Nadège
ORCID
Venue
Journal of Investigative Dermatology
Publisher
Elsevier BV
Published
2011-06
Volume
131
Issue
6
Pages
1300-1307
ISSN
0022-202X (ISSN-L)
DOI
10.1038/jid.2011.30
OpenAlex
W2016246963
Cited by
86
References
26
Citations by year
2025: 4 · 2024: 3 · 2023: 3 · 2022: 4 · 2021: 5 · 2020: 3 · 2019: 6 · 2018: 4 · 2017: 12 · 2016: 6 · 2015: 10 · 2014: 9 · 2013: 11 · 2012: 6
FWCI
4.09
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Investigative Dermatology (publishedVersion)
  • PubMed (publishedVersion)
  • HAL (submittedVersion)
Funders
  • Centre National de la Recherche Scientifique
  • Société Française de Dermatologie et de Pathologie Sexuellement Transmissible
  • Institut National de la Santé et de la Recherche Médicale
  • Ligue Contre le Cancer
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
PD-1, melanoma, cutaneous metastasis, tumor-infiltrating lymphocytes, PD-L1, T cell receptor signaling, CD8+ T cells, CD4+ T cells, tumor immune evasion, calcium response, IFN-gamma production, tumor regression, myeloid cells
MeSH terms
Aged, Aged, 80 and over, Female, Humans, Male, Melanoma, Middle Aged, Prospective Studies, Receptors, Antigen, T-Cell, Skin Neoplasms, T-Lymphocytes, Signal Transduction, Antigens, CD, Lymphocytes, Tumor-Infiltrating, B7-1 Antigen, Apoptosis Regulatory Proteins, B7-H1 Antigen, Programmed Cell Death 1 Receptor, Programmed Cell Death 1 Ligand 2 Protein

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