Angiogenesis and the immune response as targets for the prevention and treatment of colorectal cancer (Review)

Author(s):  
Ricky Sharma ◽  
Angus Dalgleish ◽  
William Steward ◽  
Kenneth O'Byrne
2015 ◽  
Vol 87 (9) ◽  
Author(s):  
Łukasz Dziki ◽  
Anna Puła ◽  
Konrad Stawiski ◽  
Barbara Mudza ◽  
Marcin Włodarczyk ◽  
...  

Abstractwas to assess patients’ awareness of the prevention and treatment of colorectal cancer.Patients diagnosed with colorectal cancer, hospitalised at the Department of General and Colorectal Surgery of the Medical University in Łódź during the period from January 2015 to April 2015, were asked to complete a questionnaire concerning their families’ medical case record, factors predisposing them to the development of colorectal cancer, the tests applied in diagnostics, and the treatment process. The questionnaire comprised 42 closed-ended questions with one correct answer. A statistical analysis of all answers was carried out.The study group consisted of 30 men and 20 women aged 27–94 years old. A strong, statistically significant negative correlation between a patient’s age and his/her awareness of the prevention and treatment of colorectal cancer was noted (p<0.001; r= −0.51). The study demonstrated a statistically significant relationship between the occurrence of neoplasms in a patient’s family (p=0.009) or, more specifically, the occurrence of colorectal cancer (p=0.008), and the awareness of the prevention programme. The women’s group was characterised by statistically significantly greater awareness of colonoscopy as a screening examination (p=0.004).Patients need more information on colorectal cancer, its risk factors, prevention, the treatment process, and postoperative care. Lack of awareness of the colorectal cancer issue can be one of the major factors contributing to the high incidence of this disease.


2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Lijun Xu ◽  
Qing Zheng

Abstract Background Tumor mutational burden (TMB) is a promising predictor, which could stratify colorectal cancer (CRC) patients based on the response to immune checkpoint inhibitors (ICIs). MicroRNAs (miRNAs) act as the key regulators of anti-cancer immune response. However, the relationship between TMB and miRNA expression profiles is not elucidated in CRC. Methods Differentially expressed miRNAs (DE miRNAs) between the TMBhigh group and the TMBlow group were identified for the CRC cohort of the TCGA database. In the training cohort, a miRNA-related expression signature for predicting TMB level was developed by the least absolute shrinkage and selection operator (LASSO) method and tested with reference to its discrimination, calibration, and decision curve analysis (DCA) in the validation cohort. Functional enrichment analysis of these TMB-related miRNAs was performed. The correlation between this miRNA-related expression signature and three immune checkpoints was analyzed. Results Twenty-one out of 43 DE miRNAs were identified as TMB-related miRNAs, which were used to develop a miRNA-related expression signature. This TMB-related miRNA signature demonstrated great discrimination (AUCtest set = 0.970), satisfactory calibration (P > 0.05), and clinical utility in the validation cohort. Functional enrichment results revealed that these TMB-related miRNAs were mainly involved in biological processes associated with immune response and signaling pathways related with cancer. This miRNA-related expression signature showed a median positive correlation with PD-L1 (R = 0.47, P < 0.05) and CTLA4 (R = 0.39, P < 0.05) and a low positive correlation with PD-1 (R = 0.16, P < 0.05). Conclusion This study presents a miRNA-related expression signature which could stratify CRC patients with different TMB levels.


2007 ◽  
Vol 15 (1-2) ◽  
pp. 5-9
Author(s):  
Attila Fenyvesi

Background: The genetic alterations in colorectal cancer (CRC) progression are determined by two separate pathways, chromosomal and microsatellite instability (MSI). The CRCs with MSI have distinct clinicopathological characteristics with pronounced tumor-associated immune responses. The aim of our study was to investigate the intensity of host immune response in CRC tissue by comparing microsatellite stable (MSS) and instable tumors. Methods: The study was performed on CRC specimens from 28 patients with MSI and compared with 30 MSS tumors. The microsatellite status was evaluated with two markers by PCR and melting point analysis. The immunostaining with anti-CD3 pan-T cell antibody was used to quantify the number of tumor infiltrating lymphocytes. The lymphocytes in peritumoral stromal and the Crohn?s-like peritumoral reaction were counted on H&E slides. Results: No significant differences were found in the average number of lymphocytes in peritumoral stroma and in clinicopathological characteristics of CRCs. The conspicuous Crohn?s-like lymphoid reactions were present in 67.86% of CRCs with MSI versus 26.66% of MSS cases. The CRCs with MSI cases carried significantly higher numbers of tumor infiltrating T-lymphocytes (13.21 versus 7.47) (p<0.0001). Conclusion: The presences of peritumoral Crohn?s-like lymphoid and intraepithelial lymphocytic reaction were intensive markers for MSI in colorectal carcinomas in our study. The peculiar genetic instability in MSI tumors may lead to a continuous production of abnormal peptides, which act as neoantigens. They could induce specific antitumor immune responses effective in limiting tumor growth and spread. Abnormal peptides are potentially promising in immunotherapy advancing and in the design of a vaccine against colorectal tumors with MSI.


2021 ◽  
Author(s):  
Stephanie L. Schmit ◽  
Ya-Yu Tsai ◽  
Joseph Bonner ◽  
Rebeca Sanz-Pamplona ◽  
Amit D. Joshi ◽  
...  

2021 ◽  
Vol 46 (2) ◽  
Author(s):  
Can Kong ◽  
Tao Fu

Author(s):  
Nurul Amir Hashim ◽  
Sharaniza Ab‑Rahim ◽  
Leny Suddin ◽  
Mohd Ahmad Saman ◽  
Musalmah Mazlan

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A880-A880
Author(s):  
Abigail Overacre-Delgoffe ◽  
Hannah Bumgarner ◽  
Anthony Cillo ◽  
Ansen Burr ◽  
Justin Tometich ◽  
...  

BackgroundColorectal cancer (CRC) is one of the most common and deadly cancers in the US, and the survival rate for advanced cases is poor. While immunotherapy has revolutionized cancer treatment, CRC remains largely unresponsive, with only ~6% of patients responding to anti-PD1. Specific microbiome signatures are associated with anti-PD1 response in melanoma patients; however, the underlying mechanism remains unclear. While the microbiome in cancer patients has been extensively studied, the endogenous immune response to these microbes and the subsequent effects on cancer immunity remain unstudied. Most microbes reside within the gut, and bacteria that adhere to the intestinal epithelium can stimulate bacteria-specific immune responses. Therefore, we hypothesized that the microbiome, especially adherent, immunogenic bacteria, may support anti-tumor immunity through activation of local microbiota-specific T cells.MethodsUsing a carcinogen-induced mouse model of CRC, we sought to determine the impact of microbiome modulation on the anti-tumor immune response. We colonized tumor-bearing mice with Helicobacter hepaticus (Hhep) and assessed tumor burden, survival, and immune infiltration. Lymphocytes were isolated from the tumor and surrounding tissue when tumors were terminal (12 weeks). We utilized TCR transgenic mice and MHC class II tetramers to track the spatial and transcriptional Hhep-specific T cell response through 5’ single cell RNAseq, flow cytometry, and spectral immunofluorescence.ResultsHhep colonization in tumor-bearing mice led to decreased tumor burden and significantly improved survival. Interestingly, colonization induced activation of Hhep-specific T follicular helper cells (TFHs) that supported formation of mature peri- or intra-tumoral tertiary lymphoid structures (TLS). The presence of TLS led to increased infiltration of cytotoxic lymphocytes (T and NK cells) within the tumor core. Surprisingly, the anti-tumor response was dependent on CD4+ T and B cells but not CD8+ T cells. Using TFH KO mice, we found that Hhep-specific CD4+ T cells were both necessary and sufficient to drive TLS maturation and anti-tumor immunity.ConclusionsHere, we demonstrate that addition of a single bacterial species after tumor formation leads to a reduction in CRC tumor burden and increased survival through TLS maturation. This microbiome-dependent remodeling of the tumor microenvironment is driven by Hhep-specific TFH cells that are both necessary and sufficient for tumor control, demonstrating for the first time that microbiota-specific T cells contribute to anti-tumor immunity. Overall, these findings suggest that microbiome modulation and the subsequent microbiota-specific CD4+ T cell response may represent a new variety of immunotherapies for cancers that remain resistant to checkpoint blockade.


Sign in / Sign up

Export Citation Format

Share Document