Time-spatial analysis of T cell receptor repertoire in esophageal squamous cell carcinoma patients treated with combined radiotherapy and PD-1 blockade

Yan, Chunhong; Ma, Xiumei; Guo, Zhoubo; Wei, Xuedong; Han, Dong; Zhang, Tian; Chen, Xi; Cao, Fuliang; Dong, Jie; Zhao, Gang; Gao, Xuan; Wang, Tao; Jiang, Yao; Wang, Ping; Pang, Qingsong; Zhang, Wencheng

doi:10.1080/2162402x.2022.2025668

Cited by 12 publications

(11 citation statements)

References 58 publications

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“…As previously described ( 23 , 34 ), we used 100 μm as the cutoff to divide PDACs into those with the shorter average distances (<100 μm) and those with the longer average distances (>100 μm) between two types of cells. Here, we did the analysis by using different cutoffs to divide PDACs into two subgroups and found that different cutoffs yielded consistent results and that the 100-μm cutoff remains the most optimal one (fig.…”

Section: Resultsmentioning

confidence: 99%

Neoadjuvant radioimmunotherapy in pancreatic cancer enhances effector T cell infiltration and shortens their distances to tumor cells

Wang,

Gai,

Zhang

et al. 2024

Sci. Adv.

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Radiotherapy is hypothesized to have an immune-modulating effect on the tumor microenvironment (TME) of pancreatic ductal adenocarcinoma (PDAC) to sensitize it to anti–PD-1 antibody (a–PD-1) treatment. We collected paired pre- and posttreatment specimens from a clinical trial evaluating combination treatment with GVAX vaccine, a–PD-1, and stereotactic body radiation (SBRT) following chemotherapy for locally advanced PDACs (LAPC). With resected PDACs following different neoadjuvant therapies as comparisons, effector cells in PDACs were found to skew toward a more exhausted status in LAPCs following chemotherapy. The combination of GVAX/a–PD-1/SBRT drives TME to favor antitumor immune response including increased densities of GZMB + CD8 + T cells, T H 1, and T H 17, which are associated with longer survival, however increases immunosuppressive M2-like tumor-associated macrophages (TAMs). Adding SBRT to GVAX/a–PD-1 shortens the distances from PD-1 + CD8 + T cells to tumor cells and to PD-L1 + myeloid cells, which portends prolonged survival. These findings have guided the design of next radioimmunotherapy studies by targeting M2-like TAM in PDACs.

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Section: Resultsmentioning

confidence: 99%

Neoadjuvant radioimmunotherapy in pancreatic cancer enhances effector T cell infiltration and shortens their distances to tumor cells

Wang,

Gai,

Zhang

et al. 2024

Sci. Adv.

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“…46 TMB is defined as the number of non-synonymous sequence genetic mutations in the coding regions of the cancer genome, usually calculated as the number of mutations per megagenome sequence. 47 TMB may drive effective antitumor immune responses and ultimately lead to sustained clinical responses to immunotherapy. 48,49 We performed TMB analysis on the model and found that the TMB was higher in the high-risk group, which confirmed the accuracy of the risk score as a predictor of immunotherapy efficacy.…”

Section: Discussionmentioning

confidence: 99%

“…Colon cancer patients with high TMB may have a better immunotherapy response than patients with low TMB 46 . TMB is defined as the number of non‐synonymous sequence genetic mutations in the coding regions of the cancer genome, usually calculated as the number of mutations per megagenome sequence 47 . TMB may drive effective antitumor immune responses and ultimately lead to sustained clinical responses to immunotherapy 48,49 .…”

Section: Discussionmentioning

confidence: 99%

Constructing and validating a risk model based on neutrophil‐related genes for evaluating prognosis and guiding immunotherapy in colon cancer

Wang,

Qiu

et al. 2024

The Journal of Gene Medicine

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BackgroundColon cancer is one of the most common digestive tract malignancies. Although immunotherapy has brought new hope to colon cancer patients, there is still a large proportion of patients who do not benefit from immunotherapy. Studies have shown that neutrophils can interact with immune cells and immune factors to affect the prognosis of patients.MethodsWe first determined the infiltration level of neutrophils in tumors using the CIBERSORT algorithm and identified key genes in the final risk model by Spearman correlation analysis and subsequent Cox analysis. The risk score of each patient was obtained by multiplying the Cox regression coefficient and the gene expression level, and patients were divided into two groups based on the median of risk score. Differences in overall survival (OS) and progression‐free survival (PFS) were assessed by Kaplan–Meier survival analysis, and model accuracy was validated in independent dataset. Differences in immune infiltration and immunotherapy were evaluated by immunoassay. Finally, immunohistochemistry and western blotting were performed to verify the expression of the three genes in the colon normal and tumor tissues.ResultsWe established and validated a risk scoring model based on neutrophil‐related genes in two independent datasets, The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database, with SLC11A1 and SLC2A3 as risk factors and MMP3 as a protective factor. A new nomogram was constructed and validated by combining clinical characteristics and the risk score model to better predict patients OS and PFS. Immune analysis showed that patients in the high‐risk group had immune cell infiltration level, immune checkpoint level and tumor mutational burden, and were more likely to benefit from immunotherapy.ConclusionsThe low‐risk group showed better OS and PFS than the high‐risk group in the neutrophil‐related gene‐based risk model. Patients in the high‐risk group presented higher immune infiltration levels and tumor mutational burden and thus may be more responsive to immunotherapy.

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“…Colon cancer patients with high TMB may have a better immunotherapy response than patients with low TMB(46). TMB is de ned as the number of nonsynonymous sequence genetic mutations in the coding regions of the cancer genome, usually calculated as the number of mutations per megagenome sequence (47). Tumor mutational burden may drive effective antitumor immune responses and ultimately lead to sustained clinical responses to immunotherapy(48, 49).…”

Section: Discussionmentioning

confidence: 99%

Construction and validation of neutrophil-related gene based risk models for assessing colon cancer prognosis and guiding immunotherapy

Sha-sha

Wang²,

Qiu

et al. 2023

Preprint

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Purpose Colon cancer is one of the most common digestive tract malignancies. Studies have shown that neutrophils can interact with immune cells and immune factors to affect the prognosis of patients. Methods We first determined the infiltration level of neutrophils in tumors using CIBERSORT and identified key genes in the final risk model by Spearman correlation analysis and subsequent Cox analysis. The risk score of each patient was obtained by multiplying the Cox regression coefficient by the gene expression level, and patients were divided into two groups according to the median. Differences in OS and PFS were assessed by KM survival analysis, and model accuracy was validated in another independent dataset. Finally, the differences in immune infiltration and immunotherapy were evaluated by immunoassay. Results We established and validated a risk scoring model based on neutrophil-related genes in two independent datasets; the patients in the high-risk group had a poorer prognosis than those in the low-risk group. A new nomogram was constructed and validated by combining clinical characteristics and the risk score model to better predict patient OS and PFS. Immune analysis showed that patients in the high-risk group had immune cell infiltration level, immune checkpoint levels, and tumor mutational burden and were more likely to benefit from immunotherapy. Conclusion The low-risk group had relatively better OS and PFS than the high-risk group in the neutrophil-related gene-based risk model. Patients in the high-risk group presented higher immune infiltration levels and tumor mutational burden and thus may be more responsive to immunotherapy.

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Time-spatial analysis of T cell receptor repertoire in esophageal squamous cell carcinoma patients treated with combined radiotherapy and PD-1 blockade

Cited by 12 publications

References 58 publications

Neoadjuvant radioimmunotherapy in pancreatic cancer enhances effector T cell infiltration and shortens their distances to tumor cells

Neoadjuvant radioimmunotherapy in pancreatic cancer enhances effector T cell infiltration and shortens their distances to tumor cells

Constructing and validating a risk model based on neutrophil‐related genes for evaluating prognosis and guiding immunotherapy in colon cancer

Construction and validation of neutrophil-related gene based risk models for assessing colon cancer prognosis and guiding immunotherapy

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