T-cell clonotypes in cancer

Straten, Per thor; Schrama, David; Andersen, Mads Hald; Becker, Jürgen C.

doi:10.1186/1479-5876-2-11

Cited by 16 publications

(12 citation statements)

References 91 publications

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“…A similar degree of TCR restriction in colorectal carcinoma tissue in comparison to normal colon tissue contrasts with the phenomenon of high proliferative oligoclonal expansions of specific T-cell populations as described for highly immunogenic malignancies such as melanoma [16]. …”

Section: Discussionmentioning

confidence: 95%

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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Section: Discussionmentioning

confidence: 95%

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

et al. 2010

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“…A repertoire of 10 15–18 various TCRs may be generated in humans ( 13 , 14 ). Therefore, the characterization of the TCR in TILs may reveal important information regarding the biologically important anti-tumor T cell responses ( 15 ). In the present study, the T cell repertoire was analyzed in blood samples and cancer tissues in advanced CRC patients that had received cancer vaccine treatment, with the aim of exploring predictive biomarkers for the efficacy prior to treatment, and for selecting of patients that are likely to exhibit better clinical outcomes.…”

Section: Introductionmentioning

confidence: 99%

Characterization of the T cell repertoire by deep T cell receptor sequencing in tissues and blood from patients with advanced colorectal cancer

et al. 2016

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The aim of the present study was to characterize infiltrated T cell clones that define the tumor immune environment and are important in the response to treatment in patients with advanced colorectal cancer (CRC). In order to explore predictive biomarkers for the efficacy of immunochemotherapies, T cell receptor (TCR) repertoire analysis was performed using blood samples and tumor tissues obtained from patients with advanced CRC that had been treated with a combination of five-cancer peptide vaccines and oxaliplatin-based chemotherapy. The TCR-α/β complementary DNAs (cDNAs), prepared from the messenger RNAs (mRNAs) obtained from 17 tumor tissues and 39 peripheral blood mononuclear cells of 9 CRC patients at various time points, were sequenced. The oligoclonal enrichment of certain TCR sequences was identified in tumor tissues and blood samples; however, only a few TCR sequences with a frequency of >0.1% were commonly detected in pre- and post-treatment tumor tissues, or in post-treatment blood and tissue samples. The average correlation coefficients of the TCR-α and TCR-β clonotype frequencies between the post-treatment tumor tissues and blood samples were 0.023 and 0.035, respectively, and were much lower compared with the correlation coefficients of the TCR-α and TCR-β clonotype frequencies between pre- and post-treatment blood samples (0.430 and 0.370, respectively), suggesting that T cell populations in tumor tissues vary from those in blood. Although the sample size was small, a tendency for the TCR diversity in tumor tissues to drastically decrease during the treatment was indicated in two patients, who exhibited a longer progression-free survival time. The results of the present study suggest that TCR diversity scores in tissues may be a useful predictive biomarker for the therapeutic effect of immunochemotherapy for patients with advanced CRC.

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“…A skewed TCR repertoire in TIL has been described in several studies [17]–[19], and in others, clonal expansion with restricted TCR repertoire was reported [16], [27]. However, many properties of TIL remain to be elucidated, including proliferation and clonality, variation of diversity, and the changing pattern of TCR subfamilies.…”

Section: Discussionmentioning

confidence: 98%

Differences in TCR-Vβ Repertoire and Effector Phenotype between Tumor Infiltrating Lymphocytes and Peripheral Blood Lymphocytes Increase with Age

Shao

Wang

et al. 2014

PLoS ONE

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Tumor infiltrating lymphocytes (TIL) reflect the host's anti-tumor immune response, and can be a valuable predictor of prognosis. However, many properties of TIL are not fully understood. In the present study, TCR-Vβ repertoires of cancer patients were primarily analyzed by flow cytometry. Abnormally expressed TCR-Vβ subfamilies were generally found in both TIL and peripheral blood lymphocytes (PBL) of each patient. Of note, increased patient age was associated with increasingly biased TCR-Vβ repertoire in TIL but not in PBL, and the dispersion degree of the differences of TCR-Vβ subfamilies between TIL and PBL correlated positively with age (P = 0.007). Utilizing immunoscope analysis, we identified the age-related reduction in TCR-Vβ diversity, but polyclonal pattern was predominant in significantly expanded TCR-Vβ subfamilies. In addition, we found that older patients possessed a decreased ratio of CD8+CD62L+ non-effector cells in TIL compared to PBL, implying age-related increase of CD8+CD62L− effector cells in TIL. The colocalization analysis of CD8 and CD3, however, suggested the suppressed activity of these effector cells in tumor microenvironment. These findings further elucidate the properties of TIL, showing an increasing difference between TIL and PBL with age, which may provide insight for the development of effective immunotherapies for cancer patients of different ages.

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T-cell clonotypes in cancer

Cited by 16 publications

References 91 publications

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

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

Characterization of the T cell repertoire by deep T cell receptor sequencing in tissues and blood from patients with advanced colorectal cancer

Differences in TCR-Vβ Repertoire and Effector Phenotype between Tumor Infiltrating Lymphocytes and Peripheral Blood Lymphocytes Increase with Age

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