التفاصيل البيبلوغرافية
| العنوان: |
Clonal Abundance of Tumor-Specific CD4+ T Cells Potentiates Efficacy and Alters Susceptibility to Exhaustion. |
| المؤلفون: |
Malandro, Nicole1,2, Budhu, Sadna1, Kuhn, Nicholas F.3, Liu, Cailian1, Murphy, Judith T.1,2, Cortez, Czrina1, Zhong, Hong1, Yang, Xia1, Rizzuto, Gabrielle1,4, Altan-Bonnet, Grégoire5, Merghoub, Taha1,6 merghout@mskcc.org, Wolchok, Jedd D.1,4,6 wolchokj@mskcc.org |
| المصدر: |
Immunity (10747613). Jan2016, Vol. 44 Issue 1, p179-193. 15p. |
| مصطلحات موضوعية: |
*CD4 antigen, *CLONING, *T cells, *DRUG synergism, *DRUG efficacy, *DISEASE susceptibility |
| مستخلص: |
Summary 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. [ABSTRACT FROM AUTHOR] |
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