What is the Current Role of Immunotherapy for Colon Cancer?

Galanternik, Fernando; Valsecchi, Matías E.; Greco, Martín; Recondo, Gonzálo; Vega, Máximo de la; Canton, Enrique Diaz

doi:10.2174/1574887111666160330121851

Cited by 5 publications

(4 citation statements)

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“…In human cancer, involvement of tumor infiltration of T cells to obtain an antitumor immune response is considered to be predictive factors, associated with long-term survival of patients. 24,38 In our strategy, RFA and local combination therapy showed a strong increase of TILs in the distant tumors.…”

Section: Discussionmentioning

confidence: 76%

“…We evaluated lymphoid cells density in distant liver metastases by automatic count, as described by Allard et al 24 Our data showed low lymphocyte densities of CD3, CD4 and CD8 on the patient tumors ( Figure 1(a)). Furthermore, lymphocyte infiltration analysis showed similar patterns for all markers in both groups; characterized by a small increase of TILs on the tumor front ( Figure 1(b)).…”

Section: Rfa Treatment Alone Did Not Increase Tils In Patients' Colormentioning

confidence: 99%

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Local immunomodulation combined to radiofrequency ablation results in a complete cure of local and distant colorectal carcinoma

et al. 2019

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Radiofrequency ablation (RFA) of colorectal liver metastases activates a specific T-cell response that is ineffective in avoiding recurrence. Recently, local immunomodulation garnered interests as a way to improve the immune response. We were interested in improving the RFA immune response priming to propose a curative treatment of colorectal cancer (CRC) based on antitumor immunity. First, we demonstrated that the RFA did not increase the tumor infiltrating lymphocytes in secondary distant tumors of patients and in mice model and could not avoid relapse. Remarkably, RFA and in situ immunomodulation with GM-CSF-BCG hydrogel induced complete cure of microscopic secondary lesions in mice, related to a strong specific immune response. Then, we demonstrated that the immune escape of large secondary lesions was reversed by addition of the systemic PD-1 blockade to the in situ immunomodulation. The lack of an effective distant immune response in patients treated with RFA confirmed the relevance of this new combination strategy. Increasing the in situ priming response of radiofrequency ablation provides effective adjuvants to induce an abscopal effect. In the case of large lesions, synergy between PD1 blockade inhibitor, ineffective alone or after single RFA, with in situ immunomodulation, could lead to reconsideration of the use of checkpoint inhibition in metastatic MSS CRC.

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Section: Discussionmentioning

confidence: 76%

Section: Rfa Treatment Alone Did Not Increase Tils In Patients' Colormentioning

confidence: 99%

Local immunomodulation combined to radiofrequency ablation results in a complete cure of local and distant colorectal carcinoma

et al. 2019

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“…In the gastrointestinal tract they are especially abundant in the neuroendocrine cells of the mucosa, suggesting a role as a gut hormone for this peptide. Previous studies confirmed that both AM and PAMP regulate many physiological and pathological conditions in the gut (Galanternik et al, 2016 ). Furthermore, AM and PAMP also act as antimicrobial peptides, constituting a defense mechanism against pathogenic bacteria (Allaker et al, 1999 ).…”

Section: Introductionmentioning

confidence: 58%

Lack of Adrenomedullin Aggravates Acute TNBS-Induced Colitis Symptoms in Mice, Especially in Females

et al. 2017

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Adrenomedullin (AM) is a biologically active peptide which has been tested as a new therapy for inflammatory bowel disease (IBD) in animal models and in patients with severe ulcerative colitis. We used an inducible knockout (KO) mouse model for AM to evaluate the effects of endogenous levels of this peptide on the development and degree of pathogenesis of IBD. Acute colitis was induced in mice of both sexes by rectal instillation of 3 mg 2,4,6-trinitrobenzenesulfonic acid (TNBS) in 100 μL of 50% ethanol. Control mice received the same volume of saline in 50% ethanol. During the following 5 days, the weight and the disease severity index of all animals were recorded. After sacrifice, the inflammatory response was macroscopically assessed by analyzing the weight of the colon; by histomorphometrical analysis on histological sections; and by qRT-PCR determination of different inflammatory, adhesion, and regeneration molecules. TNBS administration caused a significantly more severe colitis in KO mice, and especially in females, when compared to wild type (WT) animals. Abrogation of the AM gene caused more severe diarrhea, accompanied by rectal bleeding, anorexia, and a significant increase of colon weight. Histological analysis of TNBS-treated KO mice showed large areas of lymphocyte infiltrates in the mucosa and submucosa, with loss of tissue architecture. No alterations were observed in the expression levels of inflammatory cytokines at the time of sacrifice; meanwhile lack of AM resulted in lower levels of some adhesion molecules and regeneration markers. Taken together, these results support the protective role of endogenous AM against the development of acute colitis, and that its effects are particularly beneficial on females.

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“…The improving quality of life, changes in eating habits and pollution of the environment have resulted in increased incidence of colon cancer in recent years [3] . Surgery, chemotherapy, radiotherapy and immunotherapy are the four major therapeutic modalities [4] . Although the survival rate of colon cancer patients has increased thanks to advanced and improved early diagnostic and therapeutic strategies, the five-year survival rate is only about 50% worldwide [5] .…”

Section: Backgroudmentioning

confidence: 99%

MicroRNA miR-29a inhibits colon cancer progression by downregulating B7-H3 expression: potential molecular targets for colon cancer therapy

Wang

Chen

Xie

et al. 2020

Preprint

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BackgroudMiR-29a belongs to one of the subtypes of miRNAs known as non-coding single-stranded RNAs, and is preferentially expressed in normal tissues. B7-H3, a member of the B7/CD28 immunoglobulin superfamily, was shown to be overexpressed in several solid malignant tumors, including colon cancer. In addition, it is associated with tumor progression and poor prognosis.MethodsWe used immunohistochemical and western blotting to assess B7-H3 protein expression levels in colon cancer and adjacent normal tissues, and then compared their relationships with clinicopathological factors. Quantitative real time reverse transcription PCR was used to assess B7-H3 and miRNA-29a mRNA expression levels, and then their relationship and clinical significance were evaluated. In addition, colon cancer Caco-2 cells, which constitutively overexpress B7-H3, were transfected with lentivirus particles for miR-29a upregulation. Invasion and migration assays were carried out in vitro along with the establishment of a subcutaneous xenograft model in vivo to determine the role of miRNA-29a in colon cancer progression.ResultsThe B7-H3 protein showed elevated expression in colon carcinoma, and was relevant to TNM staging, lymph node metastasis and reduced survival. Meanwhile, miR-29a was preferentially expressed in normal colon tissues while B7-H3 transcript levels had no marked differences between tumor and normal tissue specimens. In vitro, miR-29a upregulation resulted in reduced B7-H3 expression. Furthermore, miR-29a upregulation reduced the invasive and migratory abilities of colon carcinoma cells. In animal models, upregulation of miR-29a slowed down the growth of subcutaneous xenotransplanted tumors, and resulted in prolonged survival time.ConclusionMiR-29a downregulates B7-H3 expression and accordingly inhibits colon cancer progression, invasion and migration, indicating miR-29a and B7-H3 might represent novel molecular targets for advanced immunotherapy in colon cancer.

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What is the Current Role of Immunotherapy for Colon Cancer?

Cited by 5 publications

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Local immunomodulation combined to radiofrequency ablation results in a complete cure of local and distant colorectal carcinoma

Local immunomodulation combined to radiofrequency ablation results in a complete cure of local and distant colorectal carcinoma

Lack of Adrenomedullin Aggravates Acute TNBS-Induced Colitis Symptoms in Mice, Especially in Females

MicroRNA miR-29a inhibits colon cancer progression by downregulating B7-H3 expression: potential molecular targets for colon cancer therapy

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