Localization-associated immune phenotypes of clonally expanded tumor-infiltrating T cells and distribution of their target antigens in rectal cancer
| Autor: | Michael Hummel, Thomas Blankenstein, Josefin Garmshausen, Klaus Dornmair, Lars Bullinger, Livius Penter, Felix Aigner, Holger Hackstein, Leo Hansmann, Kerstin Dietze, Maria Fernanda Lammoglia Cobo, Julia Ritter, Sandra Wienzek-Lischka |
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| Rok vydání: | 2019 |
| Předmět: |
lcsh:Immunologic diseases. Allergy
0301 basic medicine Cancer Research Colorectal cancer T cell Immunology clonal t cell expansion Biology cancer immunology lcsh:RC254-282 03 medical and health sciences 0302 clinical medicine Immune system Antigen medicine Immunology and Allergy t cell antigen specificity rectal cancer single cell immune phenotyping Original Research Cancer immunology human immunology t cell receptor sequencing Tumor-infiltrating lymphocytes lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens medicine.disease Molecular biology 030104 developmental biology medicine.anatomical_structure Oncology Single cell sequencing tumor-infiltrating lymphocytes 030220 oncology & carcinogenesis single cell technologies lcsh:RC581-607 CD8 |
| Zdroj: | OncoImmunology, Vol 8, Iss 6 (2019) Oncoimmunology |
| ISSN: | 2162-402X |
| DOI: | 10.1080/2162402x.2019.1586409 |
| Popis: | The degree and type of T cell infiltration influence rectal cancer prognosis regardless of classical tumor staging. We asked whether clonal expansion and tumor infiltration are restricted to selected-phenotype T cells; which clones are accessible in peripheral blood; and what the spatial distribution of their target antigens is. From five rectal cancer patients, we isolated paired tumor-infiltrating T cells (TILs) and T cells from unaffected rectum mucosa (T(UM)) using 13-parameter FACS single cell index sorting. TCRαβ sequences, cytokine, and transcription factor expression were determined with single cell sequencing. TILs and T(UM) occupied distinct phenotype compartments and clonal expansion predominantly occurred within CD8(+) T cells. Expanded TIL clones identified by paired TCRαβ sequencing and exclusively detectable in the tumor showed characteristic PD-1 and TIM-3 expression. TCRβ repertoire sequencing identified 49 out of 149 expanded TIL clones circulating in peripheral blood and 41 (84%) of these were PD-1(-) TIM-3(-). To determine whether clonal expansion of predominantly tumor-infiltrating T cell clones was driven by antigens uniquely presented in tumor tissue, selected TCRs were reconstructed and incubated with cells isolated from corresponding tumor or unaffected mucosa. The majority of clones exclusively detected in the tumor recognized antigen at both sites. In summary, rectal cancer is infiltrated with expanded distinct-phenotype T cell clones that either i) predominantly infiltrate the tumor, ii) predominantly infiltrate the unaffected mucosa, or iii) overlap between tumor, unaffected mucosa, and peripheral blood. However, the target antigens of predominantly tumor-infiltrating TIL clones do not appear to be restricted to tumor tissue. |
| Databáze: | OpenAIRE |
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