Absence of CCR2 reduces spontaneous intestinal tumorigenesis in the Apc mouse model.

The biological activities of chemokine (C-C motif) ligand 2 (CCL2) are mediated via C-C chemokine receptor-2 (CCR2). Increased CCL2 level is associated with metastasis of many cancers. In our study, we investigated the role of the CCL2/CCR2 axis in the development of spontaneous intestinal tumorigenesis using the Apc mouse model.

Immunotherapy of Primary Brain Tumors: Facts and Hopes.

The field of cancer immunotherapy has made exciting progress for some cancer types in recent years. However, recent failures of late-phase clinical trials evaluating checkpoint blockade in patients with glioblastoma (GBM) represent continued challenges for brain cancer immunotherapy. This is likely due to multiple factors including but not limited to marked genetic and antigenic heterogeneity, relatively low mutational loads, and paucity of GBM-infiltrating T cells.

Novel and shared neoantigen derived from histone 3 variant H3.3K27M mutation for glioma T cell therapy.

The median overall survival for children with diffuse intrinsic pontine glioma (DIPG) is less than one year. The majority of diffuse midline gliomas, including more than 70% of DIPGs, harbor an amino acid substitution from lysine (K) to methionine (M) at position 27 of histone 3 variant 3 (H3.3).

The yin and yang of leukotriene B mediated inflammation in cancer.

The high affinity leukotriene B receptor, BLT1 mediates chemotaxis of diverse leukocyte subsets to the sites of infection or inflammation. Whereas the pathological functions of LTB/BLT1 axis in allergy, autoimmunity and cardiovascular disorders are well established; its role in cancer is only beginning to emerge. In this review, we summarize recent findings on LTB/BLT1 axis enabling distinct outcomes toward tumor progression.

Isocitrate dehydrogenase mutations suppress STAT1 and CD8+ T cell accumulation in gliomas.

Mutations in the isocitrate dehydrogenase genes IDH1 and IDH2 are among the first genetic alterations observed during the development of lower-grade glioma (LGG). LGG-associated IDH mutations confer gain-of-function activity by converting α-ketoglutarate to the oncometabolite R-2-hydroxyglutarate (2HG). Clinical samples and gene expression data from The Cancer Genome Atlas (TCGA) demonstrate reduced expression of cytotoxic T lymphocyte-associated genes and IFN-γ-inducible chemokines, including CXCL10, in IDH-mutated (IDH-MUT) tumors compared with IDH-WT tumors.

Chemoattractant Receptors BLT1 and CXCR3 Regulate Antitumor Immunity by Facilitating CD8+ T Cell Migration into Tumors.

Immunotherapies have shown considerable efficacy for the treatment of various cancers, but a multitude of patients remain unresponsive for various reasons, including poor homing of T cells into tumors. In this study, we investigated the roles of the leukotriene B4 receptor, BLT1, and CXCR3, the receptor for CXCL9, CXCL10, and CXCL11, under endogenous as well as vaccine-induced antitumor immune response in a syngeneic murine model of B16 melanoma. Significant accelerations in tumor growth and reduced survival were observed in both BLT1(-/-) and CXCR3(-/-) mice as compared with wild-type (WT) mice.

A spontaneous metastasis model reveals the significance of claudin-9 overexpression in lung cancer metastasis.

Metastasis causes most cancer related mortality but the mechanisms governing metastatic dissemination are poorly defined. Metastasis involves egression of cancer cells from the primary tumors, their survival in circulation and colonization at the secondary sites. Cancer cell egression from the primary tumor is the least defined process of metastasis as experimental metastasis models directly seed cancer cells in circulation, thus bypassing this crucial step.

Regulation of cytotoxic T-Lymphocyte trafficking to tumors by chemoattractants: implications for immunotherapy.

Cancer immunotherapy has recently emerged as an important treatment modality. FDA approval of provenge, ipilimumab and pembrolizumab has started to deliver on the long awaited promise of cancer immunotherapy. Many new modalities of immunotherapies targeting cytotoxic T lymphocytes (CTLs) responses, such as adoptive cell therapies and vaccines, are in advanced clinical trials.

Expression of leukotriene B₄ receptor-1 on CD8⁺ T cells is required for their migration into tumors to elicit effective antitumor immunity.

Leukotriene B₄ (LTB₄) receptor (BLT)1 is expressed on variety of immune cells and has been implicated as a mediator of diverse inflammatory diseases. However, whether biological responses initiated via this receptor generate tumor-promoting inflammation or antitumor immunity remains unexplored. In this study, we investigated the role of BLT1 in antitumor immunity using syngeneic TC-1 cervical cancer model, and observed accelerated tumor growth and reduced survival in BLT1⁻/⁻ mice compared with BLT1⁺/⁺ mice.