Restriction of T cell receptor Vβ repertoire in melanoma metastasis responding to immunotherapy

Möhler, Thomas; Willhauck, M.; Scheibenbogen, Carmen; Pawlita, Michael; Bludau, H.; Brossart, Peter; Hünstein, W.; Keilholz, Ulrich

doi:10.1097/00008390-199504000-00010

Cited by 5 publications

(2 citation statements)

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“…However, our data suggest that the T cells reactive with melanoma peptide antigens may have been induced or expanded by the cytokine treatment. This is in agreement with our observation that following treatment with IFNa/IL-2 a strong overexpression of 1 to 3 T cell receptor Vb families (suggesting clonal expansion of T cells) was observed in regressing metastases (Moehler et al, 1995;Willhauck et al, 1996).…”

Section: Discussionsupporting

confidence: 93%

Analysis of the T cell response to tumor and viral peptide antigens by an IFNγ-ELISPOT assay

et al. 1997

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We have established a sensitive ELISPOT assay measuring interferon gamma (IFN gamma) release on a single-cell basis to detect influenza peptide-specific CD8+ T cells in uncultured peripheral blood mononuclear cells (PBMC). Using this method, we studied the T cell response to HLA-A1 and HLA-A2.1 binding peptide epitopes derived from the MAGE-1 and MAGE-3 proteins, from the melanoma-associated antigens tyrosinase, Melan-A/MART-1 and gp100, and from influenza proteins in stage IV melanoma patients and healthy controls. In 18 of 24 HLA-A2-positive donors (75%), but only in 9 of 25 HLA-A2-positive melanoma patients (36%) T cells reactive with the influenza matrix peptide were demonstrated (p = 0.007). T cells responding to one or several of the melanoma-associated peptides were detected in 5 of 25 HLA-A2-positive patients with metastatic melanoma. Four of these 5 patients had been treated with interleukin-2- and IFN alpha-containing therapy. Two of the 24 healthy donors had T cells reactive with the MART-1 27-35 peptide. No reactivity with the HLA-A1-binding peptides from MAGE-1 or MAGE-3 was detected in any of the HLA-A1-positive healthy controls or melanoma patients. These results show that the IFN gamma-ELISPOT assay is suitable to determine quantitatively T cells reactive with melanoma-associated and influenza peptide epitopes in uncultured PBMC. The failure to detect T cells responding to influenza in many melanoma patients with progressive disease may indicate an impairment of their T cell function.

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Section: Discussionsupporting

confidence: 93%

Analysis of the T cell response to tumor and viral peptide antigens by an IFNγ-ELISPOT assay

et al. 1997

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“…In cancer research, a restricted TCR repertoire has been found at the tumor site of various malignant diseases [28-36], and in case of melanoma, a highly restricted repertoire may be linked to regression during cytokine therapy [37]. However, it is still a matter of debate whether a restricted TCR repertoire in peripheral blood of tumor patients exists and whether such a peripheral restriction mirrows oligoclonal expansions of specific T-cells in the tumor compartment [36,38-42].…”

Section: Introductionmentioning

confidence: 99%

Comparison of T-cell receptor repertoire restriction in blood and tumor tissue of colorectal cancer patients

et al. 2010

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Several immunotherapeutic approaches rely on antigen-specific T-cells. Restrictions in the T-cell receptor (TCR) repertoire were reported as indicator of anti-tumor cytotoxic T-lymphocyte (CTL) response in various tumor entities. It is unclear yet whether a TCR restriction in peripheral blood mirrors the tumor compartment. We compared the expression of TCR Vβ-families for the quantification of TCR repertoire alterations in blood and tissue samples from patients with colorectal carcinoma. Blood samples from patients with colorectal carcinoma and healthy volunteers and tissue samples of normal colonic mucosa and colorectal carcinoma were analyzed. Relative Vβ-family quantification was performed based on quantitative reverse transcribed PCR. Standard deviation and average mean of the single families were determined. Two variables describing the degree of Vβ-repertoire restriction were defined. Forty-eight blood samples and 37 tissue samples were analyzed. TCR repertoire restriction was higher in blood of tumor patients than in blood of healthy controls (p < 0.05). No difference in the degree of TCR repertoire restriction was found between carcinoma and unaffected colon tissue. We found no corresponding elevated TCR families among the different compartments blood, normal colon, and carcinoma tissue of the same patient. In conclusion, we observed a repertoire restriction in peripheral blood as well as in tumor tissue of cancer patients. However, in tumor tissue, repertoire alterations were comparable to normal mucosa, suggesting compartment-specific TCR distribution rather than alterations due to tumor-T-cell interaction questioning the presence of highly restricted clonal T-cell expansions in colorectal cancer as they have been described in other, assumingly more immunogenic tumor entities.

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Analysis of TCR usage in human tumors: a new tool for assessing tumor-specific immune responses

Sensi

Parmiani

1995

Immunology Today

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Restriction of T cell receptor Vβ repertoire in melanoma metastasis responding to immunotherapy

Cited by 5 publications

References 0 publications

Analysis of the T cell response to tumor and viral peptide antigens by an IFNγ-ELISPOT assay

Analysis of the T cell response to tumor and viral peptide antigens by an IFNγ-ELISPOT assay

Comparison of T-cell receptor repertoire restriction in blood and tumor tissue of colorectal cancer patients

Analysis of TCR usage in human tumors: a new tool for assessing tumor-specific immune responses

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