NK Cells Stimulate Recruitment of cDC1 into the Tumor Microenvironment Promoting Cancer Immune Control

By Jan P. Böttcher, E. Bonavita, P. Chakravarty, Hanna Blees, Mar Cabeza-Cabrerizo, S. Sammicheli, N. Rogers, Erik Sahai, S. Zelenay, C. Reis e Sousa. Cell, 2018

1,581 citations recorded by the source corpus.

Summary Conventional type 1 dendritic cells (cDC1) are critical for antitumor immunity, and their abundance within tumors is associated with immune-mediated rejection and the success of immunotherapy. Here, we show that cDC1 accumulation in mouse tumors often depends on natural killer (NK) cells that produce the cDC1 chemoattractants CCL5 and XCL1. Similarly, in human cancers, intratumoral CCL5, XCL1, and XCL2 transcripts closely correlate with gene signatures of both NK cells and cDC1 and are associated with increased overall patient survival. Notably, tumor production of prostaglandin E2 (PGE2) leads to evasion of the NK cell-cDC1 axis in part by impairing NK cell viability and chemokine production, as well as by causing downregulation of chemokine receptor expression in cDC1. Our findings reveal a cellular and molecular checkpoint for intratumoral cDC1 recruitment that is targeted by tumor-derived PGE2 for immune evasion and that could be exploited for cancer therapy.

Subfields: Immunology

View Paper: https://www.semanticscholar.org/paper/387614539225c9e299b62009f6c34121cdaa2000

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In Immunology

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4. Shuang Wei
5. Yan Yu
6. Weitong Gao
7. Yang Zhou
8. Xuepeng Wang

Citations in the corpus

• Autophagy, ferroptosis, pyroptosis, and necroptosis in tumor immunotherapy (2022, background): “Further research found that PGE2 reduced the amount of DCs infiltrated into TME by suppressing chemokines CCL5 and XCL1.(329) Although the action of PGE2 and its downstream signaling has not been elaborated more detailedly, current study has provided strong evidence that PGE2 has immunosuppressive e”
• CD8+ T cells and fatty acids orchestrate tumor ferroptosis and immunity via ACSL4 (2022, background): “It is well known that PGE2 negatively affects anti-tumor immune responses and inhibition of cyclooxygenases (COX) 2 can sensitize ICB in tumor bearing animal models (Bottcher et al., 2018; Li et al., 2016; Zelenay et al., 2015).”