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RNA-Seq-Based TCR Profiling Reveals Persistently Increased Intratumoral Clonality in Responders to Anti-PD-1 Therapy
Substantial effort is being invested in the search for peripheral or intratumoral T cell receptor (TCR) repertoire features that could predict the response to immunotherapy. Here we demonstrate the utility of MiXCR software for TCR and immunoglobulin repertoire extraction from RNA-Seq data obtained...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7199218/ https://www.ncbi.nlm.nih.gov/pubmed/32411589 http://dx.doi.org/10.3389/fonc.2020.00385 |
Sumario: | Substantial effort is being invested in the search for peripheral or intratumoral T cell receptor (TCR) repertoire features that could predict the response to immunotherapy. Here we demonstrate the utility of MiXCR software for TCR and immunoglobulin repertoire extraction from RNA-Seq data obtained from sorted tumor-infiltrating T and B cells. We use this approach to extract TCR repertoires from RNA-Seq data obtained from sorted tumor-infiltrating CD4(+) and CD8(+) T cells in an HKP1 (Kras(G12D)p53(−/−)) syngeneic mouse model of lung cancer after anti-PD-1 treatment. For both subsets, we demonstrate decreased TCR diversity in response to therapy. At a later time point, repertoire diversity is restored in progressing disease but remains decreased in responders to therapy in both CD4(+) and CD8(+) subsets. These observations complement previous studies and suggest that stably increased intratumoral CD4(+) and CD8(+) T cell clonality after anti-PD-1/PD-L1 therapy could serve as a predictor of long-term response. |
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