Batf3+DCs and the 4-1BB/4-1BBL axis are required at the effector phase in the tumor microenvironment for PD-1/PD-L1 blockade efficacy

被引：5

作者：

Ziblat, Andrea ^{[1
]}

Horton, Brendan L. ^{[1
]}

Higgs, Emily F. ^{[1
]}

Hatogai, Ken ^{[1
]}

Martinez, Anna ^{[1
]}

Shapiro, Jason W. ^{[2
]}

Kim, Danny E. C. ^{[1
]}

Zha, Yuanyuan ^{[3
]}

Sweis, Randy F. ^{[4
]}

Gajewski, Thomas F. ^{[1
,4
]}

机构：

[1] Univ Chicago, Dept Pathol, Sect Hematol & Oncol, Chicago, IL 60637 USA

[2] Univ Chicago, Ctr Res Informat, Chicago, IL 60637 USA

[3] Univ Chicago, Human Immunol Monitoring Facil, Chicago, IL 60637 USA

[4] Univ Chicago, Dept Med, Chicago, IL 60612 USA

来源：

CELL REPORTS | 2024年 / 43卷 / 05期

关键词：

CD8(+) T-CELLS; DENDRITIC CELLS; ESTABLISHED TUMORS; RESPONSES; ACTIVATION; EXPRESSION; EXPANSION; MELANOMA; SAFETY; PROLIFERATION;

D O I：

10.1016/j.celrep.2024.114141

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

The cellular source of positive signals that reinvigorate T cells within the tumor microenvironment (TME) for the therapeutic efficacy of programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) blockade has not been clearly defined. We now show that Batf3-lineage dendritic cells (DCs) are essential in this process. Flow cytometric analysis, gene-targeted mice, and blocking antibody studies revealed that 4-1BBL is a major positive co-stimulatory signal provided by these DCs within the TME that translates to CD8+ + T cell functional reinvigoration and tumor regression. Immunofluorescence and spatial transcriptomics on human tumor samples revealed clustering of Batf3+ + DCs and CD8+T + T cells, which correlates with anti-PD-1 efficacy. In addition, proximity to Batf3+ + DCs within the TME is associated with CD8+ + T cell transcriptional states linked to anti-PD- 1 response. Our results demonstrate that Batf3+ + DCs within the TME are critical for PD-1/PD-L1 blockade efficacy and indicate a major role for the 4-1BB/4-1BB ligand (4-1BBL) axis during this process.

引用

页数：27

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