Crosstalk between Regulatory T Cells and Tumor-Associated Dendritic Cells Negates Anti-tumor Immunity in Pancreatic Cancer

Abstract

SUMMARY Regulatory T (Treg) cell infiltration constitutes a prominent feature of pancreatic ductal adenocarcinoma (PDA). However, the immunomodulatory function of Treg cells in PDA is poorly understood. Here, we demonstrate that Treg cell ablation is sufficient to evoke effective anti-tumor immune response in early and advanced pancreatic tumorigenesis in mice. This response is dependent on IFN-γ producing cytotoxic CD8+ T cells. We show that Treg cells engage in extended interactions with tumor-associated CD11c+ dendritic cells (DCs) and restrain their immunogenic function by suppressing the expression of costimulatory ligands necessary for CD8+ T cell activation. Consequently, tumor-associated CD8+ T cells fail to display effector activities when Treg cell ablation is combined with DC depletion. We propose that tumor-infiltrating Treg cells can promote immune-tolerance by suppressing tumor-associated DC immunogenicity. The therapeutic manipulation of this axis might provide an effective approach for the targeting of PDA.

Development and validation of a seven‐immune‐feature‐based prognostic score for oral squamous cell carcinoma after curative resection

“…Moreover, our data further revealed significant correlations in densities among those individual TIIs in either CT or IM compartment. This is quite in agreement with previous findings that corporation among diverse types of TIIs and crosstalk between cancer cells and adjacent TIIs to facilitate or inhibit tumor growth and progression …”

“…This is quite in agreement with previous findings that corporation among diverse types of TIIs and crosstalk between cancer cells and adjacent TIIs to facilitate or inhibit tumor growth and progression. 27,31,32 Prognostic significance of individual TIIs subpopulations in OSCC Until now, the correlations between various TIIs and clinical outcome as well as prognostic utilities of TIIs have been well established in a myriad of human cancers including OSCC. 9,11,29,33,34 Higher CD4 + and CD8 + TILs were associated with improved OS and relapse-free survival and served as significant independent prognostic factors for HNSCC.…”

Contrasting impact of corticosteroids on anti-PD-1 immunotherapy efficacy for tumor histologies located within or outside the central nervous system

“…26,32–36 Given this study’s findings, dexamethasone treatment could potentially have a positive influence on shaping antitumor immunity by reducing circulating Treg cell numbers and their subsequent tumor infiltration. 37 However, this potential positive influence must be counterbalanced with dexamethasone’s negative effects on conventional CD4+ and CD8+ T cells.…”

Perfluorocarbon Nanoemulsions for Combined Pulmonary siRNA Treatment of Lung Metastatic Osteosarcoma

“…The process is driven by several transcription factors, including several of the STAT family (STAT3, STAT5). [25] STAT3 activation is also involved in the accumulation and activation of Tregs. Chemokines play further role in attracting MDSCs to the tumor sites and SDF-1 is among those prominently involved.…”