Tolerance and immune suppression in the tumor microenvironment

Ostrand‐Rosenberg, Suzanne

doi:10.1016/j.cellimm.2015.09.011

Cited by 44 publications

(23 citation statements)

References 110 publications

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“…It has been reported that T lymphocytes and their associated cytokines are abnormal in patients with cancer and are significantly involved in tumor development and progression . In the present study, we found that levels of CD8 + T cells and Th1 cells in peripheral blood of patients with NSCLC were significantly decreased, whereas Treg were increased, which were consistent with the previous findings .…”

Section: Discussionsupporting

confidence: 92%

Long‐term prognostic significance of interleukin‐17‐producing T cells in patients with non‐small cell lung cancer

Wang

Chen

et al. 2019

Cancer Science

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The presence of interleukin (IL)‐17‐producing T cells has recently been reported in non‐small cell lung cancer (NSCLC) patients. However, the long‐term prognostic significance of these populations in NSCLC patients remains unknown. In the present study, we collected peripheral blood from 82 NSCLC patients and 22 normal healthy donors (NC). Percentages of IL‐17‐producing CD4+T (Th17), CD8+T (Tc17) and γδT cells (γδT17) were measured to determine their association with clinical outcomes and overall survival (OS) in NSCLC. All NSCLC patients were followed up until July 2018. Median follow‐up time was 13.5 months (range 1‐87 months). The 3‐ and 5‐year survival rate was 27% and 19.6%, respectively. We found that Th17 cells and γδT17 cells were significantly increased, whereas Tc17 cells were markedly decreased in patients with NSCLC compared with those in NC. In addition, Th17 cells were significantly positively associated with T helper type 1 cells (Th1), whereas γδT17 cells were significantly negatively associated with γδT + interferon (IFN)‐γ+ cells. High percentages of peripheral Tc17 cells were significantly associated with favorable 5‐year OS (P = .025), especially in patients with early TNM stage (P = .016). Furthermore, high percentages of peripheral Th17 cells were positively associated with favorable 5‐year OS in patients with late TNM stage (P = .002). However, no significant association was observed between γδT17 cells and OS, regardless of the TNM stage. In conclusion, our findings suggest that enhanced Th17 and reduced Tc17 cells in the peripheral blood could be a significant predictor of a favorable prognosis for NSCLC patients.

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Section: Discussionsupporting

confidence: 92%

Long‐term prognostic significance of interleukin‐17‐producing T cells in patients with non‐small cell lung cancer

Wang

Chen

et al. 2019

Cancer Science

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“…(B) J774M cells were treated with IFNg for 24 h and lysed for nuclear extract preparation. The nuclear extracts were incubated with that MDSCs massively accumulate in human cancers including colorectal cancer, [52][53][54] our findings thus raise the notion that in addition to the tumor cells, the PDL1 C MDSCs might be another major source of PD-L1 that inhibits tumor-infiltrating CTL activation and function in the tumor microenvironment. 17,55 The relative role of these PDL1 C MDSCs in colon cancer immune escape and resistance to immune checkpoint immunotherapy requires further studies.…”

Section: Discussionmentioning

confidence: 64%

The expression profiles and regulation of PD-L1 in tumor-induced myeloid-derived suppressor cells

et al. 2016

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Programmed death-ligand 1 (PD-L1) is an inhibitory ligand that binds to PD-1 to suppress T cell activation. PD-L1 is constitutively expressed and inducible in tumor cells, but the expression profiles and regulatory mechanism of PD-L1 in myeloid-derived suppressor cells (MDSCs) are largely unknown. We report that PD-L1 is abundantly expressed in tumor-infiltrating leukocytes in human patients with both microsatellite instable and microsatellite stable colon cancer. About 60% CD11b PD-L1C MDSCs are also significantly higher in tumor-bearing mice than in tumor-free mice. Interestingly, the highest PD-L1C MDSCs were observed in the tumor microenvironment in which 56-71% tumor-infiltrating MDSCs are PD-L1 C in vivo. In contrast, PD-L1 C MDSCs are significantly less in secondary lymphoid organs and peripheral blood as compared to the tumor tissues, whereas bone marrow MDSCs are essentially PD-L1¡ in tumor-bearing mice. IFNg is highly expressed in cells of the tumor tissues and IFNg neutralization significantly decreased PD-L1 C MDSCs in the tumor microenvironment in vivo. However, IFNg-activated pSTAT1 does not bind to the cd274 promoter in MDSCs. Instead, pSTAT1 activates expression of IRF1, IRF5, IRF7 and IRF8 in MDSCs, and only pSTAT1-activated IRF1 binds to a unique IRF-binding sequence element in vitro and chromatin in vivo in the cd274 promoter to activate PD-L1 transcription. Our data determine that PD-L1 is highly expressed in tumor-infiltrating MDSCs and in a lesser degree in lymphoid organs, and the pSTAT1-IRF1 axis regulates PD-L1 expression in MDSCs.

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“…Regulatory T-cells (Tregs) and tumor-associated macrophages (TAMs) comprise the majority of tumor-infiltrating cells associated with immune suppression in the tumor microenvironment [7–9]. The anti-inflammatory cytokines, interleukin-10 (IL-10), IL-4, and transforming growth factor- β 1 (TGF- β 1), mediate local immune suppression and promote increased infiltration of Tregs and TAMs.…”

Section: Introductionmentioning

confidence: 99%

Immunosuppression Induced by Chronic Inflammation and the Progression to Oral Squamous Cell Carcinoma

Sun

Liu

Guan

et al. 2016

Mediators of Inflammation

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Oral squamous cell carcinoma (OSCC) is an aggressive, invasive malignancy of epithelial origin. The progression from premalignant lesions—oral leukoplakia (OLK) and oral lichen planus (OLP)—to OSCC involves complex inflammatory processes that have not been elucidated. We investigated the roles of inflammatory mediators and infiltrating immunocytes in the pathogenic progression of OLK and OLP to OSCC. The occurrence of regulatory T-cells (Tregs) and tumor-associated macrophages (TAMs) and the expression of anti-inflammatory cytokines and proinflammatory cytokines were investigated in OLK, OLP, and OSCC tissues. Immunohistochemical staining of CD4, FOXP3, CD68, TGF-β1, IL-10, IL-4, IFN-γ, and MCP-1 showed that the occurrence of Tregs and TAMs increased in parallel with disease progression in OLK and OSCC. IL-10 gradually increased during the early stages of OLK and in OSCC. Infiltrating IL-4+ macrophages were seen with increasing frequency in OLK tissue during the progression of oral dysplasia. Fewer TGF-β1+ macrophages were seen in OSCC than in OLK and OLP. The expression of IFN-γ decreased gradually with the OLK development and had the lowest expression in OSCC. MCP-1 expression did not change significantly during the development of OSCC. The results suggested that the immunosuppression induced by chronic inflammation promotes tumorigenesis in OSCC, rather than initiating it.

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Tolerance and immune suppression in the tumor microenvironment

Cited by 44 publications

References 110 publications

Long‐term prognostic significance of interleukin‐17‐producing T cells in patients with non‐small cell lung cancer

Long‐term prognostic significance of interleukin‐17‐producing T cells in patients with non‐small cell lung cancer

The expression profiles and regulation of PD-L1 in tumor-induced myeloid-derived suppressor cells

Immunosuppression Induced by Chronic Inflammation and the Progression to Oral Squamous Cell Carcinoma

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