In:
The Journal of Immunology, The American Association of Immunologists, Vol. 198, No. 1_Supplement ( 2017-05-01), p. 79.3-79.3
Abstract:
To understand why vaccine-activated tumor-specific T cells often fail to generate antitumor effects, we have focused on studying the intrinsic attributes of two alpha fetoprotein-specific CD8 T cells (Tet212 and Tet499). We found that while Tet499 survived in vitro re-stimulation and maintained their functions, Tet212 underwent exhaustion and apoptosis. In vivo, Tet499 generated more expansion than Tet212 and stronger antitumor effects. The different antigen responsiveness and antitumor effects of Tet212 and Tet499 correlated to their activation and differentiation state. Compared to Tet212, Tet499 were in a lower activation state and contained more stem-like memory T cells (Tscm) that could undergo more expansion in vivo. Mechanistically, Tet499 TCR was more downregulated than Tet212 TCR, which may be responsible for the lower activation and differentiation state of Tet499. In contrast to the notion that TCR downregulation dampens T cell antigen reactivity, our data show that it may help T cells maintain their antigen reactivity by halting their activation and differentiation at Tscm stage and by protecting T effector cells from antigen-induced exhaustion and apoptosis. These findings indicate that the focus of cancer vaccination should be on eliciting tumor-specific T cells at earlier differentiation stage including Tscm for better antigen reactivity.
Type of Medium:
Online Resource
ISSN:
0022-1767
,
1550-6606
DOI:
10.4049/jimmunol.198.Supp.79.3
Language:
English
Publisher:
The American Association of Immunologists
Publication Date:
2017
detail.hit.zdb_id:
1475085-5
