| First Author | Malandro N | Year | 2016 |
| Journal | Immunity | Volume | 44 |
| Issue | 1 | Pages | 179-193 |
| PubMed ID | 26789923 | Mgi Jnum | J:258942 |
| Mgi Id | MGI:6142359 | Doi | 10.1016/j.immuni.2015.12.018 |
| Citation | Malandro N, et al. (2016) Clonal Abundance of Tumor-Specific CD4(+) T Cells Potentiates Efficacy and Alters Susceptibility to Exhaustion. Immunity 44(1):179-193 |
| abstractText | Current approaches to cancer immunotherapy aim to engage the natural T cell response against tumors. One limitation is the elimination of self-antigen-specific T cells from the immune repertoire. Using a system in which precursor frequency can be manipulated in a murine melanoma model, we demonstrated that the clonal abundance of CD4(+) T cells specific for self-tumor antigen positively correlated with antitumor efficacy. At elevated precursor frequencies, intraclonal competition impaired initial activation and overall expansion of the tumor-specific CD4(+) T cell population. However, through clonally derived help, this population acquired a polyfunctional effector phenotype and antitumor immunity was enhanced. Conversely, development of effector function was attenuated at low precursor frequencies due to irreversible T cell exhaustion. Our findings assert that the differential effects of T cell clonal abundance on phenotypic outcome should be considered during the design of adoptive T cell therapies, including use of engineered T cells. |
