Regulation of CD40 signaling in colon cancer cells and its implications in clinical tissues

Abstract CD40 is a member of the tumor necrosis factor receptor family. We reveal here a correlation between CD40 expression and colon cancer differentiation. Upon CD40 ligand (CD40L) binding, CD40/CD40L signaling inhibited colon cancer proliferation, induced apoptosis, stalled cells at G0/G1, and influenced cell adhesion and metastasis. Clustering analysis identified the elevation of aryl hydrocarbon receptor repressor (AHRR) expression along with activation of CD40/CD40L signaling. Examination of clinical specimens revealed that both AHR and AHRR levels correlated with colon cancer histological grade. In addition, high expression of AHRR was associated with high expression of CD40 in tumor cells, with CD40L expression being particularly high in the tumor interstitium. Real-time PCR and western blotting analysis showed that AHRR expression in colon cancer cells was up-regulated by CD40L binding. The likely mediating signaling pathways for the effects of CD40 are described herein.
Source: Cancer Immunology, Immunotherapy - Category: Cancer & Oncology Source Type: research

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In conclusion, our data show how oncogenic and tumor-suppressive drivers of cellular senescence act to regulate surveillance processes that can be circumvented to enable SnCs to elude immune recognition but can be reversed by cell surface-targeted interventions to purge the SnCs that persist in vitro and in patients. Since eliminating SnCs can prevent tumor progression, delay the onset of degenerative diseases, and restore fitness; since NKG2D-Ls are not widely expressed in healthy human tissues and NKG2D-L shedding is an evasion mechanism also employed by tumor cells; and since increasing numbers of B cells express NKG2D ...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Abstract Tumours evolve in close interaction with their microenvironment, which encompasses a continual tension between the developing tumour and the host immune system. Clinical trials have shown that appropriate enhancement of a tumour immune response can lead to long-lasting clinical responses and patient benefit. Understanding the contribution of the immune contexture, in addition to the molecular subtype across different tumour indications, is a significant knowledge gap with limited sagacity to drive rational immunotherapy combinations. To better inform clinical studies, we must first strive to understand th...
Source: Clinical Cancer Research - Category: Cancer & Oncology Authors: Tags: Clin Cancer Res Source Type: research
The human neurotropic virus JCPyV, a member of the Polyomaviridiae family, is the opportunistic infectious agent of Progressive Multifocal Leukoencephalopathy (PML), a fatal disease seen in severe immunosuppressive conditions and, during the last decade, in patients undergoing immunotherapy. JCPyV is a ubiquitous pathogen with up to 85% of the adult population word-wide exhibiting antibodies against it. Early experiments demonstrated that direct inoculation of JCPyV into the brain of different species resulted in the development of brain tumors and other neuroectodermal-derived neoplasias. Later, several reports showed the...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
ConclusionOur findings indicated that IDO1 suppressed the CD8+ T cell response in colon cancer. miR-448, as a tumor-suppressive miRNA, enhanced the CD8+ T cell response by inhibiting IDO1 expression. The results provide a theoretical basis for the development of new immunotherapy for the treatment of colon cancer.
Source: Journal for Immunotherapy of Cancer - Category: Cancer & Oncology Source Type: research
This article will highlight recent findings on the mechanism of intrinsic resistance and recent advances in clinical trials for combination-therapy.
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
We present a patient who received nivolumab for heterogeneity of right-sided metastatic colon carcinoma. Intervention: The patient was treated with nivolumab combined with chemotherapy. Outcome: The computed tomography showed mass lesion in the left lobe of liver remained stable while metastasis tumors under envelop of liver were exacerbated after 6 cycles of nivolumab combined with chemotherapy, and later regressed. Lessons: The status of mismatch repair in primary tumor and metastatic liver carcinoma is contradictory but using nivolumab demonstrated encouraging efficacy. This is the first case of pseudo progress...
Source: Medicine - Category: Internal Medicine Tags: Research Article: Clinical Case Report Source Type: research
ConclusionsIT1208 monotherapy successfully depleted CD4+ T cells with a manageable safety profile and encouraging preliminary efficacy signals, which warrants further investigations, especially in combination with immune checkpoint inhibitors.
Source: Journal for Immunotherapy of Cancer - Category: Cancer & Oncology Source Type: research
Construction of chimeric antigen receptor‑modified T cells targeting EpCAM and assessment of their anti‑tumor effect on cancer cells. Mol Med Rep. 2019 Jul 03;: Authors: Zhou Y, Wen P, Li M, Li Y, Li XA Abstract Colon cancer is a common malignancy worldwide and there is an urgent requirement to develop effective treatment strategies. In recent years, tumor immunotherapy has become a new method of effectively treating tumors. Chimeric antigen receptor (CAR) T cell technology combines the precise targeting specificity of monoclonal antibodies with the strong toxicity and persistence of cytotoxic T ce...
Source: Molecular Medicine Reports - Category: Molecular Biology Tags: Mol Med Rep Source Type: research
ConclusionIn this manuscript, we describe the development of HERA-GITRL, a true GITR agonist with a clearly defined mechanism of action. By clustering six receptor chains in a spatially well-defined manner, HERA-GITRL induces potent agonistic activity without being dependent on additional Fc γR-mediated crosslinking.
Source: Journal for Immunotherapy of Cancer - Category: Cancer & Oncology Source Type: research
Colon cancer (CC) is one of the leading causes of cancer related mortality. Research over past decades have profoundly enhanced our understanding of immunotherapy, a major clinical accomplishment, and its potential role towards treating CC. However, studies investigating the expression of these immune checkpoints, such as epithelial cell adhesion molecule (EpCAM), programmed death-1 (PD-1), and programmed death-ligand 1 (PD-L1), by peripheral blood mononuclear cells (PBMCs) is lacking. Here, high-dimensional mass cytometry (CyTOF) is used to investigate immune alterations and promising immunotherapeutic targets expression ...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
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