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Fig. 5 | BMC Cancer

Fig. 5

From: Genomic stratification based on microenvironment immune types and PD-L1 for tailoring therapeutic strategies in bladder cancer

Fig. 5

Immune environments and therapeutics used in the immune subgroups and crosstalk in the PD-L1-low-exhausted group. a The PD-L1-high-actived group: M1 macrophages and CD8+ T cells highly infiltrated the tumours. It is well established that CD8+ T cells and macrophages are required for synergistic curative activity in response to immune checkpoint antibodies. In addition, high chemosensitivity was also inhibited in this subgroup. The PD-L1-high-exhausted group: The highest infiltration of M1 macrophages and CD8+ T cells and low infiltration of activated dendritic cells. Chemotherapy or RT are needed in combination with immune checkpoint antibodies to improve antitumour responses. The PD-L1-low-actived group: The highest infiltration of Tregs and the lowest infiltration of CD8+ T cells. The high infiltration of activated dendritic cells. In addition, the PD-L1-low-actived group exhibited the lowest infiltration of M1 macrophages, which may cause low chemosensitivity. The CD40 antibody modifies macrophages to a tumouricidal phenotype. STAT3 inhibition in combination with radiation improved tumour growth delay, decreased Tregs and enhanced effector T cells and M1 macrophages, which may improve curative effects. The PD-L1-low-exhausted group: The highest infiltration of M2 macrophages, low infiltration of CD8+ T cells, high infiltration of naïve B cells, low T follicular helper cells and activated dendritic cells. Treatment with FLT3 L/poly I:C, which induces the activation of CD103+ cDC1s at tumour sites and induces the proliferation of naïve CD8 T cells and generated CTLs, has been shown to enhance antitumour responses. In addition, CNV analysis provided translational benefits in the DEG RASL11B, which may be a target for the PD-L1-low-exhausted group. b The interactions between tumour cells and stroma mediated through CXCL12 lead to activation of the PI3K and ERK1/2 pathways, which are associated with tumour viability and the active EMT pathway, promoting cell survival and metastasis. CCL2 released by CAFs and tumour cells recruits MDSCs and macrophages. TAMs, which promote the viability of tumour cells, secrete FGF, which binds with FGFR3 and supports CAF survival and activation. Furthermore, TAMs and MDSCs suppress T-cell function in the TME. Abbreviations: CCL2, chemokine (C-C motif) ligand 2; CXCL12, chemokine (C-X-C motif) ligand 12; ERK1/2, extracellular signal-regulated kinase 1/2; FGF, fibroblast growth factor; PI3K, phosphoinosid-3-kinase

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