Chronic CD27-CD70 Costimulation Promotes Type 1-Specific Polarization of Effector Tregs

Anta, Natalia Bowakim; Acolty, Valérie; Azouz, Abdulkader; Oldenhove, Guillaume; Yagita, Hideo; Léo, Oberdan; Goriely, Stanislas; Moser, Muriel

doi:10.2139/ssrn.3924613

Cited by 1 publication

(1 citation statement)

References 54 publications

(54 reference statements)

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“…3b,c). TIGIT was the only marker in the panel unaffected by CD70-KO, but this result was consistent with previous studies showing expression of TIGIT on Treg was independent of CD70-CD27 co-stimulation 38,39 . The Treg suppression assay further corroborated that CD70-KO functionally inhibited Treg suppressive activity on the proliferation of paired CD8+ T cells, echoing the above-mentioned results (Supplementary Fig.…”

Section: Cd70 Knockout In Npc Cells Alleviates Immunosuppression By I...supporting

confidence: 92%

Nasopharyngeal carcinoma cells promote regulatory T cell development and suppressive activity via CD70-CD27 interaction

et al. 2023

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Despite the intense CD8+ T-cell infiltration in the tumor microenvironment of nasopharyngeal carcinoma, anti-PD-1 immunotherapy shows an unsatisfactory response rate in clinical trials, hindered by immunosuppressive signals. To understand how microenvironmental characteristics alter immune homeostasis and limit immunotherapy efficacy in nasopharyngeal carcinoma, here we establish a multi-center single-cell cohort based on public data, containing 357,206 cells from 50 patient samples. We reveal that nasopharyngeal carcinoma cells enhance development and suppressive activity of regulatory T cells via CD70-CD27 interaction. CD70 blocking reverts Treg-mediated suppression and thus reinvigorate CD8+ T-cell immunity. Anti-CD70+ anti-PD-1 therapy is evaluated in xenograft-derived organoids and humanized mice, exhibiting an improved tumor-killing efficacy. Mechanistically, CD70 knockout inhibits a collective lipid signaling network in CD4+ naïve and regulatory T cells involving mitochondrial integrity, cholesterol homeostasis, and fatty acid metabolism. Furthermore, ATAC-Seq delineates that CD70 is transcriptionally upregulated by NFKB2 via an Epstein-Barr virus-dependent epigenetic modification. Our findings identify CD70+ nasopharyngeal carcinoma cells as a metabolic switch that enforces the lipid-driven development, functional specialization and homeostasis of Tregs, leading to immune evasion. This study also demonstrates that CD70 blockade can act synergistically with anti-PD-1 treatment to reinvigorate T-cell immunity against nasopharyngeal carcinoma.

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Section: Cd70 Knockout In Npc Cells Alleviates Immunosuppression By I...supporting

confidence: 92%

Nasopharyngeal carcinoma cells promote regulatory T cell development and suppressive activity via CD70-CD27 interaction

et al. 2023

View full text Add to dashboard Cite

show abstract

Chronic CD27-CD70 Costimulation Promotes Type 1-Specific Polarization of Effector Tregs

Cited by 1 publication

References 54 publications

Nasopharyngeal carcinoma cells promote regulatory T cell development and suppressive activity via CD70-CD27 interaction

Nasopharyngeal carcinoma cells promote regulatory T cell development and suppressive activity via CD70-CD27 interaction

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