Clonal spreading of tumor-infiltrating T cells underlies the robust antitumor immune responses

Abstract

The repertoire of tumor-infiltrating T cells is an emerging perspective for characterizing effective antitumor T-cell responses. Oligoclonal expansion of tumor T-cell repertoire has been evaluated; however, their association with antitumor effects is unclear. We demonstrated that the polyclonal fraction of the tumor-reactive T-cell repertoire consisting of relatively minor clones increased in tumor-bearing mice treated with anti-PD-L1 or anti-CD4 monoclonal antibody, which was correlated with antitumor effect. Meanwhile, the size of the oligoclonal fraction consisting of major clones remained unchanged. Moreover, the polyclonal fraction was enriched in progenitor exhausted T cells, which are essential for a durable antitumor response, and was more dependent on CCR7+ migratory dendritic cells, which are responsible for priming tumor-reactive T cells in the tumor-draining lymph nodes. These results suggest that the expansion of diverse tumor-reactive clones ("clonal spreading") is an important mechanism by which anti-PD-L1 and anti-CD4 treatments induce robust and durable antitumor T-cell responses.

CD8+T-cell memory induced by successive SARS-CoV-2 mRNA vaccinations is characterized by clonal replacement

“…TCR sequencing libraries for next-generation sequencing were prepared according to the previous report ( 52 ). In brief, mRNA in T-cell lysate was captured by 10 μL of oligo-dT immobilized Dynabeads M270 streptavidin (Thermo Fisher Scientific).…”

“…Data processing of TCRseq was performed as previously reported ( 52 ). Briefly, Adapter trimming and quality filtering of sequencing data were performed using Cutadapt-3.2 ( 53 ) and PRINSEQ-0.20.4 ( 54 ).…”

“…Raw data of single-cell TCR sequencing were processed by pipeline produced by ImmunoGeneTeqs, Inc., as described previously ( 52 ). Briefly, sequencing reads were separated by cell barcode, then adapter trimming and quality filtering of sequencing data were performed using cutadapt 3.4 ( 53 ).…”