Dataset Information

Tumor Vasculatures: A New Target for Cancer Immunotherapy.

ABSTRACT: Immune cells rely on a functional vascular network to enter tissues. In solid tumors, blood vessels are abnormal and dysfunctional and, thus, immune effector cell infiltration is impaired. Although normalizing the tumor vasculature has been shown to improve the efficacy of cancer immunotherapies, recent studies suggest that enhanced immune stimulation also, in turn, improves tumor vascular normalization. Thus, this new paradigm of immune system-tumor vasculature mutual reprogramming opens the possibility of identifying new cancer treatment strategies that combine vascular targeting and immunotherapies. Here, we highlight current evidence supporting immune system-tumor vasculature crosstalk and outline how this relationship can provide new rationales for developing more effective combination immunotherapy strategies for treating human cancers.

SUBMITTER: Liu Z

PROVIDER: S-EPMC7925217 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Tumor Vasculatures: A New Target for Cancer Immunotherapy.

Liu Zhigang Z Wang Yifan Y Huang Yuhui Y Kim Betty Y S BYS Shan Hong H Wu Depei D Jiang Wen W

Trends in pharmacological sciences 20190720 9

Immune cells rely on a functional vascular network to enter tissues. In solid tumors, blood vessels are abnormal and dysfunctional and, thus, immune effector cell infiltration is impaired. Although normalizing the tumor vasculature has been shown to improve the efficacy of cancer immunotherapies, recent studies suggest that enhanced immune stimulation also, in turn, improves tumor vascular normalization. Thus, this new paradigm of immune system-tumor vasculature mutual reprogramming opens the po ...[more]

PMID: 31331639

Similar Datasets

Project description:Insulin-like growth factor binding protein-7 (IGFBP7) was recently reported to be a ligand of CD93, a potential target to normalize vasculature and attenuate immunotherapy. However, its role in the tumor microenvironment (TME) and immunotherapy response of bladder cancer (BLCA) remains unclear. We comprehensively evaluated the correlation between IGFBP7 and multiple immunological characteristics of BLCA across The Cancer Genome Atlas (TCGA) and two external cohorts. Importantly, the response of IGFBP7-grouped BLCA patients to immunotherapy was predicted and validated by five real-word immunotherapy cohorts. Finally, we developed an IGFBP7-based immune risk model validated by five independent cohorts. IGFBP7 modulated the TME across pan-caners. In BLCA, high expression of IGFBP7 was correlated with more aggressive clinical features. IGFBP7 was positively associated with immunomodulators and promoted tumor-infiltrating lymphocyte trafficking into the tumor microenvironment. However, T cells recognition and tumor cell killing were lower in the high-IGFBP7 group. In addition, high expression of IGFBP7 displayed lower enrichment scores for most pro-immunotherapy pathways. Clinical data from IMvigor210 and GSE176307 indicated that IGFBP7 negatively correlated with the BLCA immunotherapy response. The same trend was also observed in a renal cell carcinoma (RCC) cohort and two melanoma cohorts. Notably, urothelial and luminal differentiation were less frequently observed in the high-IGFBP7 group, while neuroendocrine differentiation was more frequently observed. Mechanistically, high IGFBP7 was associated with an enriched hypoxia pathway and higher expression of key genes in ERBB therapy and antiangiogenic therapy. Furthermore, our IGFBP7-based immune risk model was able to predict the prognosis and response to immunotherapy with good accuracy (5-year AUC = 0.734). Overall, IGFBP7 plays a critical role in the immunoregulation and TME of BLCA and may serve as a novel potential target for combination treatment with immunotherapy for BLCA.

Dataset Information

Tumor Vasculatures: A New Target for Cancer Immunotherapy.

Publications

Tumor Vasculatures: A New Target for Cancer Immunotherapy.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets