The Duplex Interaction of Microbiome with Chemoradiation and Immunotherapy: Potential Implications for Colorectal Cancer

AbstractPurpose of reviewGut microbiota has the ability to modify the metabolism of wide array of therapeutic drugs. Current treatment modalities used in colorectal cancer have a narrow therapeutic index with a side effects profile that decreases tolerance to these treatments and adversely affects treatment outcome. Harnessing the gut microbiota ability to modify oncotherapeutic drugs metabolism and hence efficacy, could be potentially used to improve treatment outcomes in colorectal cancer patients. This review will shed lights on important findings from recent microbiome interaction studies which would hopefully serve as a useful tool to guide future translative colorectal cancer research.Recent findingsRecent advances in microbiome studies have revealed an interesting aspect of gut microbes ’ carcinogenic properties in dysbiotic gut environment. Microbiota niche in colorectal cancer can also modify efficacy and toxicity profile of different oncotherapeutic treatment modalities from chemoradiotherapy to immunotherapy. Conversely, each of these treatment modalities has numerous effects on the gastrointestinal flora, causing changes in the gut microbial community that affects host morbidity and mortality.SummarySymbiotic gut microbiota is an incredible functioning organ that maintains essential aspects of our homeostasis and immunity. According to the recent body of literature, they also can modify efficacy of many therapeutic drugs including oncotherapy. Considering th...
Source: Current Colorectal Cancer Reports - Category: Cancer & Oncology Source Type: research

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ConclusionsOnly 3 out of 612 non-silent mutations encoded for neoantigens that were detectable by MS. Although MS has sensitivity limits and biases, and likely underestimated the true neoantigen burden, this established a lower bound of the percentage of non-silent mutations that encode for presented neoantigens, which may be as low as 0.5%. This could be a reason for the poor responses of non-hypermutated CRCs to immune checkpoint inhibitors. MEK-inhibitors recently failed to improve checkpoint-inhibitor efficacy in CRC and the observed lack of HLA upregulation or improved peptide presentation may explain this.
Source: Journal for Immunotherapy of Cancer - Category: Cancer & Oncology Source Type: research
Tim-3 suppresses the killing effect of Vγ9Vδ2 T cells on colon cancer cells by reducing perforin and granzyme B expression. Exp Cell Res. 2019 Nov 11;:111719 Authors: Li X, Lu H, Gu Y, Zhang X, Zhang G, Shi T, Chen W Abstract Gamma delta (γδ) T cell-based tumor immunotherapy has been one of the most promising cancer immunotherapeutic strategies. However, the key regulators of the Vγ9Vδ2 T cell-mediated antitumor response remain unclear. Recently, mounting reports have indicated that Tim-3 performs critical roles in the regulation of the activities of immune c...
Source: Experimental Cell Research - Category: Cytology Authors: Tags: Exp Cell Res Source Type: research
ConclusionsThe present case supports the efficacy of immune checkpoint inhibition in mCRC with heterogeneity in MMR/microsatellite instability status. Clinical issues that may arise in these rare patients are discussed in detail.
Source: Journal for Immunotherapy of Cancer - Category: Cancer & Oncology Source Type: research
Conclusions: The GOLFIG regimen is a reliable underestimated therapeutic option in pre-treated mCRC patients and offers a strong rationale to design further trials.
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
In this report, targeted single-cell RNA sequencing was performed on 5T4p17-specific T-cell clones to sequence the highly variable complementarity-determining region 3 (CDR3) of T-cell receptor α chain (TRA) and β chain (TRB) genes. Full-lengthTRA andTRB sequences were cloned into lentiviral vectors and transduced into CD8+ T-cells from healthy donors. Redirected effector T-cell function against 5T4p17 was measured by cytotoxicity and cytokine release assays. Seven uniqueTRA-TRB pairs were identified. All seven TCRs exhibited high expression on CD8+ T-cells with transduction efficiencies from 59 to 89%. TCR-tran...
Source: Cancer Immunology, Immunotherapy - Category: Cancer & Oncology Source Type: research
i H Abstract Cancer immunotherapy with immune checkpoint inhibitors (ICIs) such as programmed death ligand-1 (PD-L1) blockers offers pronounced clinical benefit with durable responses and a manageable safety profile. Patients with a high risk of immune-related adverse events are generally excluded from clinical trials testing ICI therapy. Thus, only a little information on the safety and clinical outcome of patients treated with an ICI after allogeneic haematopoietic cell transplantation (HCT) is currently available. Here, we report the characteristics and outcomes of six patients with, respectively, clear cell re...
Source: Swiss Medical Weekly - Category: General Medicine Authors: Tags: Swiss Med Wkly Source Type: research
This article will provide a practical concise overview of the current landscape of immunotherapy in CRC for the practicing oncologist along with a representative case presentation from our community oncology practice. PMID: 31661153 [PubMed - in process]
Source: Oncology (Williston Park, N.Y.) - Category: Cancer & Oncology Authors: Tags: Oncology (Williston Park) Source Type: research
We present here a DL based method to enumerate and quantify the immune infiltration in colorectal and breast cancer bulk RNA-Seq samples starting from scRNA-Seq. Our method makes use of a Deep Neural Network (DNN) model that allows quantification not only of lymphocytes as a general population but also of specific CD8+, CD4Tmem, CD4Th and CD4Tregs subpopulations, as well as B-cells and Stromal content. Moreover, the signatures are built from scRNA-Seq data from the tumor, preserving the specific characteristics of the tumor microenvironment as opposite to other approaches in which cells were isolated from blood. Our method...
Source: Frontiers in Genetics - Category: Genetics & Stem Cells Source Type: research
CONCLUSIONS: Collectively, these data demonstrate that the synergistic combination of entinostat, N-803, and vaccine elicits potent anti-tumor activity by generating a more inflamed TME. These findings thus form the rationale for the use of this combination of agents for patients harboring poorly or non-inflamed solid carcinomas. PMID: 31645354 [PubMed - as supplied by publisher]
Source: Clinical Cancer Research - Category: Cancer & Oncology Authors: Tags: Clin Cancer Res Source Type: research
AbstractDiffusing alpha-emitters radiation therapy (DaRT) is the only known method for treating solid tumors with highly destructive alpha radiation. More importantly, as a monotherapy, DaRT has been shown to induce a systemic antitumor immune response following tumor ablation. Here, immunomodulatory strategies to boost the antitumor immune response induced by DaRT, and the response specificity, were investigated in the colon cancer CT26 mouse model. Local treatment prior to DaRT,  with the TLR3 agonist poly I:C, was sufficient to inhibit tumor growth relative to poly I:C or DaRT alone. DaRT used in combination with t...
Source: Cancer Immunology, Immunotherapy - Category: Cancer & Oncology Source Type: research
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