An update on colorectal cancer microenvironment, epigenetic and immunotherapy

Jin, Ketao; Ren, Chengcheng; Liu, Yuyao; Lan, Huanrong; Wang, Zhen

doi:10.1016/j.intimp.2020.107041

Cited by 66 publications

(52 citation statements)

References 124 publications

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“…Colorectal cancer is one of the most significant medical challenges and has a very poor 5-year survival rate [ 1 , 2 ]. The poor prognosis for colorectal cancer is mainly due to the difficulty of making an early diagnosis, resistance to therapies and a high probability of tumor recurrence after treatments [ 3 , 4 ].…”

Section: Introductionmentioning

confidence: 99%

“…For example, immune checkpoint inhibitors currently approved by the FDA for marketing, including monoclonal antibodies against PD-1 or CTLA-4, have been successfully applied in the clinical treatment of a variety of cancers [ 13–15 ]. However, immunotherapy has no significant inhibitory effect on colorectal cancer, which is mainly due to immune escape and the inability of effector cells of the immune system to effectively enter the tumor microenvironment, specifically manifested as dense fibrotic tissue, scarce cytotoxic T lymphocytes, and natural killer cells, as well as upregulated regulatory T cells and myelogenous suppressor cells, which together cause immunosuppression, thus making colorectal cancer refractory [ 2 ]. In addition, upregulation of NF-κB expression may form an immunosuppressive tumor microenvironment in various types of cancer.…”

Section: Introductionmentioning

confidence: 99%

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RETRACTED ARTICLE: Combination therapy with Nab-paclitaxel and the interleukin-15 fused with anti-human serum albumin nanobody as a synergistic treatment for colorectal cancer

Wang

Tian

et al. 2022

Bioengineered

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This study determines the effect of Nab-paclitaxel in combination with IL-15 fusion protein, containing IL-15 and an anti-HSA nanobody domain, on colorectal cancer bearing mice. In vitro binding test of IL15 fusion protein to HSA and Nab-paclitaxel, as well as CTLL-2 cell stimulation assay were performed. The tumor inhibitory effects of Nab-paclitaxel in combination with IL-15 fusion protein was evaluated in the HCT116 bearing murine model. Moreover, the population and function of cytotoxic T cells and M1 macrophages, as well as MDSCs and Treg cells, were also further examined. As a result, combination therapy of Nab-paclitaxel and IL-15 fusion protein effectively inhibits the tumor growth and produced a 78% reduction in tumor size for HCT116, as compared to vehicle group. In the TDLN for the combination group, there were 18% of CD8+ IFN-γ + T-cells and 0.47% CD4 + CD25 + FOXP3 + regulatory T-cells, as opposed to 5.0% and 5.1%, respectively, for the model control group. Combination therapy further exhibited enhanced suppressive effects on the accumulation of CD11b + GR-1 + MDSC in spleen and bone marrow. Furthermore, Nab-paclitaxel and IL-15 fusion protein showed a significant suppression of NF-κB-mediated immune suppressive markers and increased expression of CD8, Granzyme B, CD62L, CD49b, and CD86 without obvious organ toxicity. In conclusion, combination therapy of Nab-paclitaxel and IL-15 fusion protein can effectively stimulate the antitumor activity of immune effector cells, thereby inhibiting immunosuppressive cells within the TME of colorectal cancer, and the overall therapeutic effect has a significant advantage over monotherapy. Abbreviations Interleukin 15, IL-15; Human serum albumin, HSA; Myeloid-derived suppressor cells, MDSC; Albumin binding domain, ABD; Tumor drainage lymph node, TDLN; Natural killer (NK); Tumor-draining lymph node (TDLN); Tumor infiltrating lymphocyte, TIL; Immunogenic cell death, ICD; Enhanced permeability retention, EPR; Liposomal doxorubicin, Doxil; 5-fluorouracil, 5-FU.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

RETRACTED ARTICLE: Combination therapy with Nab-paclitaxel and the interleukin-15 fused with anti-human serum albumin nanobody as a synergistic treatment for colorectal cancer

Wang

Tian

et al. 2022

Bioengineered

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“…When K-RAS gene is mutated, its expression is not regulated by EGFR signal, which leads to abnormal proliferation and metastasis of tumor cells, and then leads to resistance of patients to EGFR inhibitor drugs [9][10][11][12]. In recent years, with the advent of oxaliplatin and irinotecan, new modes of administration, new chemotherapy drugs, and new combination regimens, new breakthroughs have been made in the treatment of metastatic CRC, especially in the aspect of molecular targeted therapy [13,14]. Patients with advanced CRC combined with standard chemotherapy regimens can achieve a higher resection rate of liver metastases in unresectable patients, which can achieve significant survival improvement.…”

Section: Introductionmentioning

confidence: 99%

Analysis of Efficacy, Safety, and Prognostic Factors of mFOLFOX6 Regimen Combined with Cetuximab and Simvastatin in the Treatment of K-RAS Mutant Colorectal Cancer

Liu

2021

Evidence-Based Complementary and Alternative Medicine

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Colorectal cancer (CRC) is one of the most common malignant tumors with high morbidity and mortality. The early symptoms are latent, and most patients are in the middle or late stage when they are diagnosed. The best opportunity for surgery has been lost, and surgical resection has failed to achieve good results. In clinical practice, targeted therapy or chemotherapy is usually the main treatment. The mFOLFOX6 regimen is a standardized regimen for the treatment of advanced CRC. The main drugs in this regimen are oxaliplatin and 5-fluorouracil (5-FU). Patients with advanced CRC combined with standard chemotherapy regimens can achieve a higher resection rate of liver metastases in unresectable patients, which can achieve significant survival improvement. Therefore, in this study, oxaliplatin + calcium folinate + 5-Fu + mFOLFOX6 regimen was combined with cetuximab and simvastatin to treat CRC patients, and the clinical efficacy and prognosis were analyzed, as well as the prognostic factors. The results showed that the addition of simvastatin on the basis of conventional mFOLFOX6 regimen combined with cetuximab chemotherapy could effectively improve the efficacy, reduce the total incidence of adverse reactions, improve the overall survival rate, and prolong the overall survival time of patients. Pathological grade and peritoneal metastasis were the factors affecting the mean survival time of CRC patients.

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“…Both the tumor characteristics and the patient conditions affect the composition of the TME, subsequently dictating disease progression, responsiveness to cancer treatments and survival prognosis. Indeed, the primary tumor’s specific genetic and epigenetic alterations, its localization (i.e., ascending, transverse or descending colon, or rectum) and the hosting organs in case of metastasis strongly impact the composition of the TME [ 19 , 20 , 21 ]. Furthermore, the patient’s genetic pre-disposition, co-morbidities, bowel pre-conditions (e.g., inflammatory bowel diseases) or lifestyle (e.g., diet, physical activities, smoking) similarly alter the TME [ 22 ].…”

Section: Overview Of Colorectal Tumor Subtypes and Associated Immune ...mentioning

confidence: 99%

Molecular Mechanisms of Tumor Immunomodulation in the Microenvironment of Colorectal Cancer

Plundrich

Chikhladze

Fichtner‐Feigl

et al. 2022

IJMS

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Colorectal cancer remains one of the most important health challenges in our society. The development of cancer immunotherapies has fostered the need to better understand the anti-tumor immune mechanisms at play in the tumor microenvironment and the strategies by which the tumor escapes them. In this review, we provide an overview of the molecular interactions that regulate tumor inflammation. We particularly discuss immunomodulatory cell-cell interactions, cell-soluble factor interactions, cell-extracellular matrix interactions and cell-microbiome interactions. While doing so, we highlight relevant examples of tumor immunomodulation in colorectal cancer.

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An update on colorectal cancer microenvironment, epigenetic and immunotherapy

Cited by 66 publications

References 124 publications

RETRACTED ARTICLE: Combination therapy with Nab-paclitaxel and the interleukin-15 fused with anti-human serum albumin nanobody as a synergistic treatment for colorectal cancer

RETRACTED ARTICLE: Combination therapy with Nab-paclitaxel and the interleukin-15 fused with anti-human serum albumin nanobody as a synergistic treatment for colorectal cancer

Analysis of Efficacy, Safety, and Prognostic Factors of mFOLFOX6 Regimen Combined with Cetuximab and Simvastatin in the Treatment of K-RAS Mutant Colorectal Cancer

Molecular Mechanisms of Tumor Immunomodulation in the Microenvironment of Colorectal Cancer

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