TCF-1+ PD-1+ CD8+T cells are associated with the response to PD-1 blockade in non-small cell lung cancer patients

Xia, Fang; Wu, Gang; Hua, Jing; Zhao, Pei; Shan, Mengtian; Wang, Na; Zeng, Yu; Ding, Tingting; Zhu, Hailong; Zhu, Xuyou; Zhang, Long; Liu, Yuting; Zheng, Ling; Yi, Xianghua; Gao, Shaoyong

doi:10.1007/s00432-021-03845-7

Cited by 7 publications

(11 citation statements)

References 29 publications

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“…However, a closer look at a cellular subset level, identified T CM and PD-1+ CD8+ T cell subsets as significantly increased in responders, highlighting the importance of subset level analysis. It is also worth noting that CD8+ T cells expressing both TCF-1 and PD-1 have been found to be the key initiators of response to anti-PD1 therapy in both pre-clinical models and in human cancers (22, 23). Importantly, these cells were largely found within the tumour draining lymph nodes (18).…”

Section: Discussionmentioning

confidence: 99%

Spatial mapping reveals unique cellular interactions and enhanced tertiary lymphoid structures in responders to anti-PD-1 therapy in mucosal head and neck cancers

Ferguson,

Beddow,

Patrick

et al. 2024

Preprint

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Survival in recurrent/metastatic head and neck mucosal squamous cell carcinoma (HNmSCC) remains poor. Anti-programmed death (PD)-1 therapies have demonstrated improved survival with lower toxicity when compared to standard chemotherapy. However, response to anti-PD-1 therapy remains modest, at 13-17%. We evaluated the tumor microenvironment (TME) using Imaging Mass Cytometry (IMC) on 27 tumor specimens from 24 advanced HNmSCC patients prior to receiving anti-PD-1 based treatment. We show significantly increased central memory T cells and B cells in responders (n=8) when compared to non-responders (n=16). Spatial mapping identified interactions between phenotypically distinct malignant squamous cells with CD8+ T cells, CD4+ Tregs and endothelial cells in responders, and avoidance of these cells in non-responders. Importantly, regional analysis shows responders have more abundant tertiary lymphoid structures (TLS), with TLS proportion >20% also associated with longer progression free survival. Together these findings define the immune landscape associated with response to anti-PD-1 treatment in HNmSCCs.

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Section: Discussionmentioning

confidence: 99%

Spatial mapping reveals unique cellular interactions and enhanced tertiary lymphoid structures in responders to anti-PD-1 therapy in mucosal head and neck cancers

Ferguson,

Beddow,

Patrick

et al. 2024

Preprint

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“…Although the concept of resilient T cells in response to cancer immunotherapy has been conceived recently (4,12,55), no markers have been defined to identify them in patients with advanced cancers. Our study suggest that CX3CR1 + CD8 + T cells with low MMP can be used as a surrogate marker of resilient T cells, based on several features we identified in this report, such as (i) their CTL function (degranulation/CD107a expression) can be recovered quickly after radiotherapy; (ii) they maintain a low profile of glycolysis but produce optimal levels of ATP via mitochondrial respiration; (iii) they are not prone to exhaustion due to lower expression of PD-1 and TOX; (iv) they share a feature of stemlike T cells (TCF-1 + PD-1 + ) that allow them to be responsive again to ICI therapy (14,(53)(54)(55)(56)(57); (v) they maintain a relative lower level of ROS to avoid exhaustion but do not compromise T cell activation ( 49); (vi) they up-regulate ME1 expression to balance energy needs and redox state. Among these unique features of resilient T cells, it is important to point out that ME1 expression is not only a T cell biomarker for T cell resiliency but also a potential therapeutic target in cancer immunotherapy.…”

Section: Discussionmentioning

confidence: 99%

Salvage therapy expands highly cytotoxic and metabolically fit resilient CD8 ⁺ T cells via ME1 up-regulation

Gicobi,

Mao,

DeFranco

et al. 2023

Sci. Adv.

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Patients with advanced cancers who either do not experience initial response to or progress while on immune checkpoint inhibitors (ICIs) receive salvage radiotherapy to reduce tumor burden and tumor-related symptoms. Occasionally, some patients experience substantial global tumor regression with a rebound of cytotoxic CD8 + T cells. We have termed the rebound of cytotoxic CD8 + T cells in response to salvage therapy as T cell resilience and examined the underlying mechanisms of resilience. Resilient T cells are enriched for CX3CR1 + CD8 + T cells with low mitochondrial membrane potential, accumulate less reactive oxygen species (ROS), and express more malic enzyme 1 (ME1). ME1 overexpression enhanced the cytotoxicity and expansion of effector CD8 + T cells partially via the type I interferon pathway. ME1 also increased mitochondrial respiration while maintaining the redox state balance. ME1 increased the cytotoxicity of peripheral lymphocytes from patients with advanced cancers. Thus, preserved resilient T cells in patients rebound after salvage therapy and ME1 enhances their resiliency.

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“…Likewise, Fang et al. reported that a higher frequency of TCF-1+PD-1+CD8+ T cells was significantly related to the beneficial response to PD-1 blockade ( 57 ). Therefore, the infiltration of CD8+ T cells and expression of ICI-related genes was a good indicator in assessing response to ICI treatment.…”

Section: Discussionmentioning

confidence: 99%

Landscape of prognosis and immunotherapy responsiveness under tumor glycosylation-related lncRNA patterns in breast cancer

Tan

Zhou

et al. 2022

Front. Immunol.

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Aberrant glycosylation, a post-translational modification of proteins, is regarded to engage in tumorigenesis and malignant progression of breast cancer (BC). The altered expression of glycosyltransferases causes abnormal glycan biosynthesis changes, which can serve as diagnostic hallmarks in BC. This study attempts to establish a predictive signature based on glycosyltransferase-related lncRNAs (GT-lncRNAs) in BC prognosis and response to immune checkpoint inhibitors (ICIs) treatment. We firstly screened out characterized glycosyltransferase-related genes (GTGs) through NMF and WGCNA analysis and identified GT-lncRNAs through coexpression analysis. By using the coefficients of 8 GT-lncRNAs, a risk score was calculated and its median value divided BC patients into high-and low-risk groups. The analyses unraveled that patients in the high-risk group had shorter survival and the risk score was an independent predictor of BC prognosis. Besides, the predictive efficacy of our risk score was higher than other published models. Moreover, ESTIMATE analysis, immunophenoscore (IPS), and SubMAP analysis showed that the risk score could stratify patients with distinct immune infiltration, and patients in the high-risk group might benefit more from ICIs treatment. Finally, the vitro assay showed that MIR4435-2HG might promote the proliferation and migration of BC cells, facilitate the polarization of M1 into M2 macrophages, enhance the migration of macrophages and increase the PD-1/PD-L1/CTLA4 expression. Collectively, our well-constructed prognostic signature with GT-lncRNAs had the ability to identify two subtypes with different survival state and responses to immune therapy, which will provide reliable tools for predicting BC outcomes and making rational follow-up strategies.

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TCF-1+ PD-1+ CD8+T cells are associated with the response to PD-1 blockade in non-small cell lung cancer patients

Cited by 7 publications

References 29 publications

Spatial mapping reveals unique cellular interactions and enhanced tertiary lymphoid structures in responders to anti-PD-1 therapy in mucosal head and neck cancers

Spatial mapping reveals unique cellular interactions and enhanced tertiary lymphoid structures in responders to anti-PD-1 therapy in mucosal head and neck cancers

Salvage therapy expands highly cytotoxic and metabolically fit resilient CD8 ⁺ T cells via ME1 up-regulation

Landscape of prognosis and immunotherapy responsiveness under tumor glycosylation-related lncRNA patterns in breast cancer

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TCF-1+ PD-1+ CD8+T cells are associated with the response to PD-1 blockade in non-small cell lung cancer patients

Cited by 7 publications

References 29 publications

Spatial mapping reveals unique cellular interactions and enhanced tertiary lymphoid structures in responders to anti-PD-1 therapy in mucosal head and neck cancers

Spatial mapping reveals unique cellular interactions and enhanced tertiary lymphoid structures in responders to anti-PD-1 therapy in mucosal head and neck cancers

Salvage therapy expands highly cytotoxic and metabolically fit resilient CD8 + T cells via ME1 up-regulation

Landscape of prognosis and immunotherapy responsiveness under tumor glycosylation-related lncRNA patterns in breast cancer

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Salvage therapy expands highly cytotoxic and metabolically fit resilient CD8 ⁺ T cells via ME1 up-regulation