Cancer

Experimental challenges to modeling prostate cancer heterogeneity

Tumor heterogeneity plays a key role in prostate cancer prognosis, therapy selection, relapse, and acquisition of treatment resistance. Prostate cancer presents a heterogeneous diversity at inter- and intra-tumor and inter-patient levels which are influenced by multiple intrinsic and/or extrinsic factors. Recent studies have started to characterize the complexity of prostate tumors and these different tiers of heterogeneity. In this review, we discuss the most common factors that contribute to tumoral diversity.

Interleukin enhancer-binding factor 2 promotes cell proliferation and DNA damage response in metastatic melanoma

1q21.3 amplification, which is frequently observed in metastatic melanoma, is associated with cancer progression. Interleukin enhancer-binding factor 2 (ILF2) is located in the 1q21.3 amplified region, but its functional role or contribution to tumour aggressiveness in cutaneous melanoma is unknown.In silico analyses were performed using the TCGA SKCM dataset with clinical annotations and three melanoma microarray cohorts from the GEO datasets. RNA in situ hybridisation and immunohistochemistry were utilised to validate the gene expression in melanoma tissues.

Response to anti-DKK1 therapy in uterine carcinosarcoma: A case report

Targeted therapies are being increasingly used in clinical practice and trials. However, tumor heterogeneity among sites of metastatic disease can occur creating a conundrum when utilizing biomarker directed therapies. Here we demonstrate a patient with recurrent uterine carcinosarcoma whose local recurrence and metastatic recurrence had a varied response to paclitaxel in combination with DKN-01, a monoclonal antibody against DKK1, a modulator of Wnt/β-catenin and PI3K/AKT signaling pathways. This may be explained by differences in mutational profile found between the two sites.

Abstract LBA020: Targeting FGFR2c isoform, a novel therapeutic target with FGFR inhibitor in endometrial cancer

PURPOSE: Endometrial cancer (EC) is the most frequently diagnosed gynaecological cancer. The majority of women with EC are treated surgically and have a good outcome, however 25-30% of patients presenting with metastases or recurrent disease do not have effective therapies and have

Immune cell and tumor cell-derived CXCL10 is indicative of immunotherapy response in metastatic melanoma

A T cell-inflamed tumor microenvironment is characterized by the accumulation and local activation of CD8+ T cells and Bat3-lineage dendritic cells, which together are associated with clinical response to anti-programmed cell death protein 1 (anti-PD-1)-based immunotherapy. Preclinical models have demonstrated a crucial role for the chemokine CXCL10 in the recruitment of effector CD8+ T cells into the tumor site, and a chemokine gene signature is also seen in T cell-inflamed tumors from patients. However, the cellular source of CXCL10 in human solid tumors is not known.

Gut bacteria identified in colorectal cancer patients promote tumourigenesis via butyrate secretion

Emerging evidence is revealing that alterations in gut microbiota are associated with colorectal cancer (CRC). However, very little is currently known about whether and how gut microbiota alterations are causally associated with CRC development. Here we show that 12 faecal bacterial taxa are enriched in CRC patients in two independent cohort studies. Among them, 2 Porphyromonas species are capable of inducing cellular senescence, an oncogenic stress response, through the secretion of the bacterial metabolite, butyrate.

Characterisation of tumour microenvironment remodelling following oncogene inhibition in preclinical studies with imaging mass cytometry

Mouse models are critical in pre-clinical studies of cancer therapy, allowing dissection of mechanisms through chemical and genetic manipulations that are not feasible in the clinical setting. In studies of the tumour microenvironment (TME), multiplexed imaging methods can provide a rich source of information. However, the application of such technologies in mouse tissues is still in its infancy. Here we present a workflow for studying the TME using imaging mass cytometry with a panel of 27 antibodies on frozen mouse tissues.

Comparison of the Clinicopathologic Features and T-Cell Infiltration of B7-H3 and B7-H4 Expression in Triple-negative Breast Cancer Subtypes

Previously we revealed an upregulated expression of B7-H3 and B7-H4 mRNA and protein in breast cancer, including triple-negative breast cancer (TNBC). However, little is known regarding the clinical impact and value of B7-H3 and B7-H4 in TNBC subtypes. Thus, this study evaluated the clinicopathologic effects of B7-H3 and B7-H4 mRNA and protein expression according to the TNBC subtypes. RNAscope in situ hybridization and immunohistochemistry of B7-H3 and B7-H4 was done for 186 TNBC samples using tissue microarray.

Identification of high protein kinase CK2α in HPV(+) oropharyngeal squamous cell carcinoma and correlation with clinical outcomes

Background Oropharyngeal squamous cell carcinoma (OPSCC) incidence is rising worldwide, especially human papillomavirus (HPV)-associated disease. Historically, high levels of protein kinase CK2 were linked with poor outcomes in head and neck squamous cell carcinoma (HNSCC), without consideration of HPV status. This retrospective study examined tumor CK2α protein expression levels and related clinical outcomes in a cohort of Veteran OPSCC patient tumors which were determined to be predominantly HPV(+).

Clinical impact of Fn-induced high expression of KIR2DL1 in CD8 T lymphocytes in oesophageal squamous cell carcinoma

To analyze the correlation between the inducing effect of Fusobacterium nucleatum (Fn) on the surface expression of the inhibitory receptor KIR2DL1 on CD8+ T cells in oesophageal squamous cell carcinoma (ESCC) and the clinicopathological features and survival prognosis and to explore its clinical significance.The inducing effect of Fn on CD8+ T cell surface inhibitory receptor KIR2DL1 expression was analyzed in a coculture system of human CD8+ T cells and ESCC cells infected with Fn.

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