Journal
JOURNAL OF IMMUNOLOGY
Volume 169, Issue 9, Pages 4811-4821Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.169.9.4811
Keywords
-
Categories
Funding
- NCI NIH HHS [R01 CA78263, R01 CA89511] Funding Source: Medline
Ask authors/readers for more resources
Tumor-specific effector T cells (TE) are naturally sensitized within the L-selectin(low) (CD62(low)) fraction of tumor-draining lymph nodes (TDLN). Whether isolated from day 9 (D9) or day 12 (D12) TDLN, 5 million L-selectin(low) T-E could be culture activated and adoptively transferred to achieve complete rejection of established intradermal, pulmonary, and brain tumors. Surprisingly,, although 25 million unfractionated T cells from D9 TDLN were equally effective, even 100 million unfractionated T cells from D12 TDLN seldom prevented lethal intradermal tumor progression, despite a pronounced therapeutic excess of TE. This highly reproducible treatment failure was due to cotransfer of tumor-induced, L-selectin(high) suppressor T cells (T-S) which were also present in D12 TDLN. In contrast, D9 TDLN and normal spleens lacked L-selectin high T-S Only those L-selectin high D12 TDLN T cells that down-regulated L-selectin during culture activation were suppressive in vivo and in vitro, and, like L-selectin(low) T-E, trafficked promptly into tumors following i.v. administration. This is the first demonstration that adoptive immunotherapy can fail as a direct result of passenger T-S that share certain phenotypic and trafficking features of T-S even when otherwise curative doses of T-S have been administered. Furthermore, in contrast to recently described CD4(+)CD25(+) T-S and plasmacytoid dendritic cell-activated T-S, tumor-induced L-selectin high T-S prevent tumor rejection via blockade of sensitized, activated TE rather than via afferent blockade.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available