CoChat
Sign Up
Cited by 158T-cell and B-cell ImmunologyCancer Immunotherapy and BiomarkersImmunotherapy and Immune Responses

Rapid turnover of the CD8(+)CD28(−) T-cell subset of effector cells in the circulation of patients with head and neck cancer

Open access
Tsukishiro, Takashi, Donnenberg, Albert D., Whiteside, Theresa L.·2003·Cancer Immunology, Immunotherapy
DOI 10.1007/s00262-003-0395-6PMC PMC11032778
Open this paper in CoChat — free account

Abstract

CD8(+) T cells in the circulation of patients with head and neck cancer (HNC) were previously shown to be significantly more sensitive to, and preferentially targeted for, apoptosis than CD4(+) T cells (Hoffmann et al., Clin Cancer Res, 8:2553-2562, 2002). To distinguish global from CD8(+) subset-specific apoptosis, we studied Annexin-binding to naïve, memory, and effector subsets of CD8(+) cells by multicolor flow cytometry. Age-related changes in naïve and effector CD8(+) cell subsets were observed in patients and normal controls (NC). The frequencies of naïve (CD28(+)CD45RO(-)) CD8(+) T cells were lower and those of memory (CD28(+)CD45RO(+)) and effector (CD28(-)) CD8(+) T cells significantly higher in the circulation of HNC patients relative to age-matched NC. Among CD8(+) T cells, the CD28(-) effector cell subset contained the highest proportion of Annexin-binding cells, while the naïve CD28(+)CD45RO(-) subset contained the lowest. This suggested a high turnover rate of the CD8(+)CD28(-) effector cell subset in patients with HNC, which was being compensated by a rapid transition of naïve CD8(+) T cells to the effector cell pool. Following tumor resection, the frequency of CD8(+)CD28(-) T cells normalized in the patients, an indication that the presence of tumor had an influence on the size of CD8(+)CD28(-) T-cell pool. Ex vivo, in mixed lymphocyte-tumor cultures (MLTC) with semiallogeneic T cells as responders, CD8(+)CD28(-) T cells could be generated from CD8(+)CD28(+) cells by repeated stimulations with tumor cells. These CD8(+)CD28(-) effector cells lysed the tumor, produced IFN-gamma in response to the tumor, and strongly expressed granzyme B. Thus, the high rate of their apoptosis in the circulation of patients with HNC might be expected to contribute to tumor progression. However, the ex vivo generation of this cell subset was suppressed by strong CD28/B7 ligation or by overexpresson of MHC molecules on tumor cells, suggesting that adequate costimulation is necessary for protection from apoptosis. It appears that interactions of immune and tumor cells might determine the fate of this terminally differentiated effector cell subset.

Integrity signals

Registry

Crossref · 10.1007/s00262-003-0395-6

Cites

38 of 38 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

We couldn’t retrieve this paper’s full text, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Related

Authors
Tsukishiro, T., Donnenberg, A. D., & Whiteside, T. L.
Affiliations
University of Pittsburgh (US)
Corresponding author
Whiteside, Theresa L.
ORCID
Venue
Cancer Immunology, Immunotherapy
Publisher
Springer Science and Business Media LLC
Published
2003-10-01
Volume
52
Issue
10
Pages
599-607
ISSN
  • 0340-7004 (ISSN-L)
  • 1432-0851
DOI
10.1007/s00262-003-0395-6
PMC
PMC11032778
OpenAlex
W1972315079
Cited by
158
References
38
Citations by year
2026: 1 · 2025: 5 · 2024: 8 · 2023: 3 · 2022: 9 · 2021: 17 · 2020: 7 · 2019: 6 · 2018: 5 · 2017: 5 · 2016: 10 · 2015: 8 · 2014: 9 · 2013: 8 · 2012: 7
FWCI
2.49
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • Cancer Immunology Immunotherapy (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Cancer Institute (R01-1CA82016)
  • National Institute of Dental and Craniofacial Research (P01DE012321, P01-1-DE12321)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
  • Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
  • Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
Keywords
head and neck cancer, CD8+ T cells, T cell apoptosis, T cell turnover, naive T cells, memory T cells, CD28/B7 costimulation, tumor resection, granzyme B, interferon-gamma, tumor immunology
MeSH terms
Adult, Aged, Carcinoma, Squamous Cell, Cytotoxicity, Immunologic, Flow Cytometry, Head and Neck Neoplasms, Humans, Middle Aged, Case-Control Studies, T-Lymphocyte Subsets, Apoptosis, Annexin A5, Leukocyte Common Antigens, CD28 Antigens, CD8-Positive T-Lymphocytes

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 ›

Are you an author, or do you see a problem with this page? Request a review