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- W4313385634 abstract "Abstract We have previously shown that not all PD-1+ cells are exhausted and that PD-1 is differentially expressed on two distinct T-cell subpopulations, with high expression on T follicular helper cells and dim expression on exhausted T cells. We observed that while PD-1bright T cells lacked the ability to produce cytokines and granules, PD-1dim T cells from biopsy specimens of B-cell NHL were the major source of cytokine and granule production compared to PD-1− T cells, suggesting that PD-1dim are functionally active. Therefore, other markers are needed to more clearly identify exhausted intratumoral T cells. We first phenotyped intratumoral PD-1+ (brightly- and dimly-stained) T cells and found that LAG-3 was exclusively expressed on dimly-stained PD-1+ T cells, forming a defined population of intratumoral PD-1+LAG-3+ T cells. We found that LAG-3 expression was strongly upregulated on CD4+ or CD8+ T cells by IL-12, a cytokine that has been shown to induce T-cell exhaustion. Functionally, with a substantial numbers of PD-1dim T cells being cytokine- or granule-producing cells, it is PD-1dimLAG-3−, but not PD-1dimLAG-3+, T cells that were responsible for the capacity of producing cytokines and granules. Supporting this finding, we found that blockade of both PD-1 and LAG-3 signaling by using the combination of PD-1 and LAG-3 blocking antibodies increased cytokine production by T cells significantly more than PD-1 or LAG-3 antibody alone, suggesting that LAG-3 is important in the impairment of PD-1+ T cells. Taken together, these results suggest that constitutive expression of LAG-3 was critically involved in and defines the exhaustion of PD-1+ T cells in B-cell NHL." @default.
- W4313385634 created "2023-01-06" @default.
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- W4313385634 date "2016-05-01" @default.
- W4313385634 modified "2023-10-16" @default.
- W4313385634 title "Constitutive expression of LAG-3 defines the exhaustion of intratumoral PD-1+ T cells in B-cell non-Hodgkin lymphoma" @default.
- W4313385634 doi "https://doi.org/10.4049/jimmunol.196.supp.72.12" @default.
- W4313385634 hasPublicationYear "2016" @default.
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