CD8+ T cell exhaustion and cancer immunotherapy

Liao, Guobin; Tang, Jun; Bai, Jianying

doi:10.1016/j.canlet.2022.216043

Cited by 61 publications

(29 citation statements)

References 260 publications

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“…Prolonging the survival benefits of patients with unresectable advanced HCC has been an unsolved problem. Although multikinase inhibitors [2,3] and immune checkpoint inhibitors [4][5][6] achieve promising outcomes in the treatment of advanced HCC, high levels of interpatient heterogeneity leave few patients with sensitive responses [7], implying the complexity Ivyspring International Publisher of mechanisms that facilitate HCC progression and emphasizing the urgency to identify novel mechanisms for optimal therapeutic options.…”

Section: Introductionmentioning

confidence: 99%

LncRNA CRNDE Drives the Progression of Hepatocellular Carcinoma by inducing the Immunosuppressive Niche

Li,

Liang,

Fei

et al. 2024

Int. J. Biol. Sci.

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As a crucial protumorigenic long noncoding RNA, colorectal tumor differential expression (CRNDE) has been confirmed to facilitate the progression of various cancers. However, its role in the tumor microenvironment (TME) of hepatocellular carcinoma (HCC) is still unclear. Here we determined that CRNDE was upregulated in HCC samples and that CRNDE-positive cells were predominantly enriched in malignant tumor cells. In vivo functional assays revealed that CRNDE-induced tumor cells supported HCC progression, recruited abundant granulocyte myeloid-derived suppressor cells (G-MDSCs) and restricted the infiltration of T cells. In terms of mechanisms, CRNDE bound with Toll-like receptor 3 (TLR3) and activated NF-κB signaling to increase the secretion of c-x-c motif chemokine ligand 3 (CXCL3). CRNDE knockdown could significantly suppress the accumulation of G-MDSCs and enhance the infiltration of T cells in the TME of HCC in vivo. Taken together, our study reveals the CRNDE-NF-κB-CXCL3 axis plays a crucial role in driving the immunosuppressive niche to facilitate HCC progression by recruiting G-MDSCs.

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Section: Introductionmentioning

confidence: 99%

LncRNA CRNDE Drives the Progression of Hepatocellular Carcinoma by inducing the Immunosuppressive Niche

Li,

Liang,

Fei

et al. 2024

Int. J. Biol. Sci.

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“…T-cell exhaustion is a progressive developmental process and T ex are heterogeneous (3)(4)(5). When encountering sustained tumor antigens, naïve T-cells undergo dynamic epigenetic remodeling, differentiate to a plastic reprogrammable chromatin state, and finally transform into a fixed dysfunctional chromatin state (6).…”

Section: Introductionmentioning

confidence: 99%

Decitabine priming increases anti–PD-1 antitumor efficacy by promoting CD8+ progenitor exhausted T cell expansion in tumor models

Li¹,

Dong²,

Chang³

et al. 2023

Journal of Clinical Investigation

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CD8 + exhausted T-cells (T ex ) are heterogeneous. PD-1 inhibitors reinvigorate progenitor T ex , which subsequently differentiate into irresponsive terminal T ex .Maintaining durable proliferative capacity of progenitor T ex is important but remains unclear. Here, we showed that low-dose DNA demethylating agent decitabine-pretreated CD8 + progenitor T ex had enhanced proliferation and effector function against tumors after anti-PD-1 treatment in vitro. Decitabine-plus-anti-PD-1 treatment promoted the activation and expansion of tumor-infiltrated CD8 + progenitor T ex and efficiently suppressed tumor growth in multiple tumor models.Transcriptional and epigenetic profiling of tumor-infiltrated T cells demonstrated that decitabine-plus-anti-PD-1 combination markedly elevated the clonally expansion and cytolytic activity of progenitor T ex compared with anti-PD-1 monotherapy and restrained CD8 + T-cell terminal differentiation. Strikingly, decitabine-plus-anti-PD-1 sustained the expression and activity of AP-1 transcription factor JunD, which was reduced following PD-1 blockade therapy. Downregulation of JunD repressed T cell proliferation and activating JNK/AP-1 signaling in CD8 + T-cells enhanced the antitumor capacity of PD-1 inhibitors. Together, epigenetic agent remodels CD8 + progenitor T ex and improves responsiveness to anti-PD-1 therapy.

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“…Similarly, increased risks of lung and breast cancer were shown at lower CD8+ T-cell counts (3). Due to depleted accounts, failure in immune surveillance and elevated Notch receptors in patients with malignant tumors, CD8+T cells fail to effectively clear tumor cells, leading to immune escape and tumor progression (4)(5)(6)(7). The immune dysfunction or even immune non-response of decreased T lymphocyte subsets was suggested as a key factors potentially in the transition from benign prostatic hyperplasia to prostate cancer(8).…”

Section: Introductionmentioning

confidence: 99%

Circulating lymphocytes in Relation to Long-term Clinical Outcome in Patients with Prostate Cancer

Chen

et al. 2023

Preprint

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Background: The clinical outcomes of prostate cancer (PC) may involve changes in immune profiles. Whether long-term prognosis of PC is related to circulating lymphocytes is still uncertain. Therefore, we investigated the long-term prognostic value of different lymphocyte populations in PC. Materials: Patients with a pathological diagnosis of PC, at the Gleason Grades of 5 to 10 were included in the prospective cohort study. Lymphocyte count was evaluated in peripheral blood by flow cytometry. The prognostic value of different lymphocytes was analyzed in the whole cohort and the Kaplan-Meier method and Cox regression models were used for survival curves and multivariate analysis, respectively. Results: Between January 2001 and June 2021, 94 evaluable patients with prostate cancer were prospectively enrolled. The median follow-up duration of the study was 98 months. The levels of the CD4(+)/CD8(+) ratio, CD19(+), and CD19(+)CD5(−) B lymphocytes in non-survivors were lower than those in survivors. Grouping by each cutoff point of the lymphocytes respectively, the lower level of total CD3(+) T cells, CD3(+)CD4(+) T cells, the CD4(+)/CD8(+) ratio, total CD19(+) B cells, CD19(+)CD5(+) B cells, CD19(+)CD5(-) B cells showed poor survival. Multivariate Cox regression analysis confirmed the worse prognosis associated with higher PSA (HR=2.493, 95%CI: 1.356-4.584, P=0.003), lower CD3(+)CD4(+) T lymphocytes (HR=0.379, 95%CI: 0.170-0.843, P=0.017), lower total CD19(+) B cell (HR=0.398, 95%CI:0.187-0.845, P=0.016) and higher CD3(-)CD16(+)CD56(+) NK cells(HR=2.355, 95%CI: 1.175-4.723, P=0.016). Conclusion: Our results showed that low level of CD4(+) T lymphocytes, decreased CD19(+) B cell and high level of NK cells were correlated with poor survival, which indicates that B lymphocytes, CD4(+) T lymphocytes and NK cells might involve in prostate cancer and associated with the long-term prognosis of this elderly patients.

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CD8+ T cell exhaustion and cancer immunotherapy

Cited by 61 publications

References 260 publications

LncRNA CRNDE Drives the Progression of Hepatocellular Carcinoma by inducing the Immunosuppressive Niche

LncRNA CRNDE Drives the Progression of Hepatocellular Carcinoma by inducing the Immunosuppressive Niche

Decitabine priming increases anti–PD-1 antitumor efficacy by promoting CD8+ progenitor exhausted T cell expansion in tumor models

Circulating lymphocytes in Relation to Long-term Clinical Outcome in Patients with Prostate Cancer

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