| First Author | Burger ML | Year | 2021 |
| Journal | Cell | Volume | 184 |
| Issue | 19 | Pages | 4996-5014.e26 |
| PubMed ID | 34534464 | Mgi Jnum | J:310998 |
| Mgi Id | MGI:6765217 | Doi | 10.1016/j.cell.2021.08.020 |
| Citation | Burger ML, et al. (2021) Antigen dominance hierarchies shape TCF1(+) progenitor CD8 T cell phenotypes in tumors. Cell 184(19):4996-5014.e26 |
| abstractText | CD8 T cell responses against different tumor neoantigens occur simultaneously, yet little is known about the interplay between responses and its impact on T cell function and tumor control. In mouse lung adenocarcinoma, we found that immunodominance is established in tumors, wherein CD8 T cell expansion is predominantly driven by the antigen that most stably binds MHC. T cells responding to subdominant antigens were enriched for a TCF1(+) progenitor phenotype correlated with response to immune checkpoint blockade (ICB) therapy. However, the subdominant T cell response did not preferentially benefit from ICB due to a dysfunctional subset of TCF1(+) cells marked by CCR6 and Tc17 differentiation. Analysis of human samples and sequencing datasets revealed that CCR6(+) TCF1(+) cells exist across human cancers and are not correlated with ICB response. Vaccination eliminated CCR6(+) TCF1(+) cells and dramatically improved the subdominant response, highlighting a strategy to optimally engage concurrent neoantigen responses against tumors. |
