David Shihong Gao

mTORC1 suppression by Trp53 mutation drives resistance to immune checkpoint blockade

Alireza Labani‐Motlagh, Yang Li, David Shihong Gao, Eunseuk Lee et autres

Abstract p53 is a critical tumor suppressor gene that inhibits cancer development by regulating cell cycle arrest, apoptosis, DNA repair, and metabolism. However, recent studies examining TP53 mutations in cancer immunotherapy have yielded inconsistent results, likely due to differences in t umor …

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mTORC1 Suppression by Trp53 Mutation Drives Resistance to Immune Checkpoint Blockade

Binfeng Lu, Alireza Labani‐Motlagh, Yang Li, David Shihong Gao et autres

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Amphiregulin couples IL1RL1 + regulatory T cells and cancer-associated fibroblasts to impede antitumor immunity

Runzi Sun, Hongyu Zhao, David Shihong Gao, Andrew Ni et autres

Regulatory T (T reg ) cells and cancer-associated fibroblasts (CAFs) jointly promote tumor immune tolerance and tumorigenesis. The molecular apparatus that drives T reg cell and CAF coordination in the tumor microenvironment (TME) remains elusive. Interleukin 33 (IL-33) has been shown to …

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Figure S4 from Synergism Between IL21 and Anti-PD-1 Combination Therapy is Underpinned by the Coordinated Reprogramming of the Immune Cellular Network in the Tumor Microenvironment

Shaoxian Wu, Hao Huang, Runzi Sun, David Shihong Gao et autres

Supplementary Figure 4. IL21-anti-HSA and PD-1 mAbs synergy at the proliferation is due to upregulation of IL21R by PD-1 mAbs treatment and IL21 directly promotes proliferation on IL21R+ CD8+ T cells.

FIGURE 7 from Synergism Between IL21 and Anti-PD-1 Combination Therapy is Underpinned by the Coordinated Reprogramming of the Immune Cellular Network in the Tumor Microenvironment

Shaoxian Wu, Hao Huang, Runzi Sun, David Shihong Gao et autres

Combination therapy synergistically promoted monocyte to the M1 trajectory in the TME. A, Pseudotime plot of macrophage subsets constructed by Monocle 3. B, UMAP showing macrophages, neutrophils, and monocytes. C, Bar plot of the proportions of the above cell subsets. D, Dot …

FIGURE 6 from Synergism Between IL21 and Anti-PD-1 Combination Therapy is Underpinned by the Coordinated Reprogramming of the Immune Cellular Network in the Tumor Microenvironment

Shaoxian Wu, Hao Huang, Runzi Sun, David Shihong Gao et autres

Combination therapy enhances DC activation and maturation. A, UMAP showing DC subsets, including mDC, cDC1, cDC2, pDC. B, DC subset proportions bar graph. C–E, Heat map showing the expression of selected DEGs in cDC1, cDC2, mDC cells under different treatment conditions. F, …

Figure S1 from Synergism Between IL21 and Anti-PD-1 Combination Therapy is Underpinned by the Coordinated Reprogramming of the Immune Cellular Network in the Tumor Microenvironment

Shaoxian Wu, Hao Huang, Runzi Sun, David Shihong Gao et autres

Supplementary Figure 1. Distribution of CD4+ T cell subsets.

Figure S3 from Synergism Between IL21 and Anti-PD-1 Combination Therapy is Underpinned by the Coordinated Reprogramming of the Immune Cellular Network in the Tumor Microenvironment

Shaoxian Wu, Hao Huang, Runzi Sun, David Shihong Gao et autres

Supplementary Figure 3. IL21-anti-HSA/anti-PD-1 leads to altered immune cell populations in the tumor microenvironment.

FIGURE 1 from Synergism Between IL21 and Anti-PD-1 Combination Therapy is Underpinned by the Coordinated Reprogramming of the Immune Cellular Network in the Tumor Microenvironment

Shaoxian Wu, Hao Huang, Runzi Sun, David Shihong Gao et autres

IL21 is produced by both CXCR5+ Tfh cells and hyperactivated/exhausted CD4+ T cells in the TME. A and B, Dot plots and UMAPs showing the expression of selected genes in different CD4+ T-cell subsets in integrated human cancer tissues. C and D, …

FIGURE 4 from Synergism Between IL21 and Anti-PD-1 Combination Therapy is Underpinned by the Coordinated Reprogramming of the Immune Cellular Network in the Tumor Microenvironment

Shaoxian Wu, Hao Huang, Runzi Sun, David Shihong Gao et autres

IL21-anti-HSA/PD-1 mAbs combination therapy alters T-cell function and increases T-cell clonal expansion. A, UMAP showing CD8+ T-cell subsets, including exhausted, cycling, stem-like, effector, and IFN-induced. B, Pseudotime plot of CD8+ T-cell subsets constructed by Monocle3. C, Contour heat map of CD8+ T-cell …

FIGURE 2 from Synergism Between IL21 and Anti-PD-1 Combination Therapy is Underpinned by the Coordinated Reprogramming of the Immune Cellular Network in the Tumor Microenvironment

Shaoxian Wu, Hao Huang, Runzi Sun, David Shihong Gao et autres

IL21 is induced by anti-PD-1 mAb and is required for the antitumor efficacy of PD-1 blockade immunotherapy. A, Genome tracks of aggregate scATAC-seq data at the Il21 locus, clustered by different treatment conditions. B, Dot plot showing Il21 expression in CD4+ T …

FIGURE 5 from Synergism Between IL21 and Anti-PD-1 Combination Therapy is Underpinned by the Coordinated Reprogramming of the Immune Cellular Network in the Tumor Microenvironment

Shaoxian Wu, Hao Huang, Runzi Sun, David Shihong Gao et autres

IL21-anti-HSA and anti-PD-1 mAb administration drives phenotypic polarization and clonal expansion of Treg cells. A, UMAP showing Treg cell subsets, including pre-eTreg cells, eTreg cells, and cycling Treg cells. B, Contour heat map of Treg cell subsets split by different treatment conditions. …