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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Oncoimmunology
2016 ; 5
(10
): e1200778
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gab.com Text
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English Wikipedia
Tumor-infiltrating Tim-3(+) T cells proliferate avidly except when PD-1 is
co-expressed: Evidence for intracellular cross talk
#MMPMID27853635
Li J
; Shayan G
; Avery L
; Jie HB
; Gildener-Leapman N
; Schmitt N
; Lu BF
; Kane LP
; Ferris RL
Oncoimmunology
2016[]; 5
(10
): e1200778
PMID27853635
show ga
Programmed Death 1 (PD-1) and T cell Ig and mucin domain-3 protein (Tim-3) are
immune checkpoint receptors highly expressed on tumor infiltrating T lymphocytes
(TIL). PD-1 inhibits T cell activation and type-1 T cell responses, while Tim-3
is proposed to mark more extensively exhausted cells, although the mechanisms
underlying Tim-3 function are not clear. Trials of anti-PD-1 therapy have
identified a large subset of non-responder patients, likely due to expression of
alternative checkpoint molecules like Tim-3. We investigated the phenotypic and
functional characteristics of T cells with differential expression of PD-1
(high/low) and Tim-3 (positive/negative), using TIL directly isolated from head
and neck squamous cell carcinomas (HNSCC). Unexpectedly, we found that expression
of Tim-3 alone does not necessarily mark TIL as dysfunctional/exhausted. In
Tim-3-TIL, PD-1 levels correlate with T cell dysfunction, with a
PD-1(low/intermed) phenotype identifying recently activated and still functional
cells, whereas PD-1(hi)Tim-3(-) T cells are actually exhausted. Nonetheless,
PD-1(intermed) cells are still potently suppressed by PD-L1. PD-1 expression was
associated with reduced phosphorylation of ribosomal protein S6 (pS6), whereas
Tim-3 expression was associated with increased pS6. Using a novel mouse model for
inducible Tim-3 expression, we confirmed that expression of Tim-3 does not
necessarily render T cells refractory to further activation. These results
suggest the existence of PD-1 and Tim-3 crosstalk in regulating antitumor T cell
responses, with important implications for anti-PD-1 immunotherapy.