Advances in immunotyping of colorectal cancer

Wu, Yinhang; Zhuang, Jing; Qu, Zhanbo; Yang, Xi; Han, Shuwen

doi:10.3389/fimmu.2023.1259461

Cited by 5 publications

(2 citation statements)

References 107 publications

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“…Tumor-infiltrating lymphocytes and macrophages are key components of the immune response within the tumor microenvironment. Tumor-infiltrating lymphocytes are immune cells that infiltrate the tumor and can exhibit anti-tumor activity, while macrophages can have both pro- and anti-tumor functions depending on their polarization state [ 45 , 46 ]. Emerging evidence suggests that the composition and activity of Tumor-infiltrating lymphocytes and macrophages in the tumor microenvironment can influence tumor progression and response to therapy.…”

Section: Discussionmentioning

confidence: 99%

Immune landscape in APC and TP53 related tumor microenvironment in colon adenocarcinoma: A bioinformatic analysis

Zabeti Touchaei,

Vahidi,

Samadani

2024

EuJMI

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IntroductionAPC and TP53 are the two most regularly mutated genes in colon adenocarcinoma (COAD), especially in progressive malignancies and antitumoral immune response. The current bioinformatics analysis investigates the APC and TP53 gene expression profile in colon adenocarcinoma as a prognostic characteristic for survival, particularly concentrating on the correlated immune microenvironment.MethodsClinical and genetic data of colon cancer and normal tissue samples were obtained from The Cancer Genome Atlas (TCGA)-COAD and Genotype-Tissue Expression (GTEx) online databases, respectively. The genetic differential expressions were analyzed in both groups via the one-way ANOVA test. Kaplan–Meier survival curves were applied to estimate the overall survival (OS). P < 0.05 was fixed as statistically significant. On Tumor Immune Estimation Resource and Gene Expression Profiling Interactive Analysis databases, the linkage between immune cell recruitment and APC and TP53 status was assessed through Spearman's correlation analysis.ResultsAPC and TP53 were found mutated in 66.74% and 85.71% of the 454 and 7 TCGA-COAD patients in colon and rectosigmoid junction primary sites, respectively with a higher log2-transcriptome per million reads compared to the GTEx group (318 samples in sigmoid and 368 samples in transverse). Survival curves revealed a worse significant OS for the high-APC and TP53 profile colon. Spearman's analysis of immune cells demonstrated a strong positive correlation between the APC status and infiltration of T cell CD4+, T cell CD8+, NK cell, and macrophages and also a positive correlation between status and infiltration of T cell CD4+, T cell CD8+.ConclusionsAPC and TP53 gene mutations prevail in colon cancer and are extremely associated with poor prognosis and shortest survival. The infiltrating T cell CD4+, T cell CD8+, NK cell, and macrophages populate the colon microenvironment and regulate the mechanisms of tumor advancement, immune evasion, and sensitivity to standard chemotherapy. More comprehensive research is needed to demonstrate these results and turn them into new therapeutic outlooks.

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Section: Discussionmentioning

confidence: 99%

Immune landscape in APC and TP53 related tumor microenvironment in colon adenocarcinoma: A bioinformatic analysis

Zabeti Touchaei,

Vahidi,

Samadani

2024

EuJMI

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“…Contrastingly, the MSS CRC, majorly referred to as an "immune cold" cancer type, are predisposed by various molecular factors contributing to the underlying resistance to immunotherapy[ 161 ]. MSS-CRC is characterized by larger chromosomal aberrations that mark the phenotype of MSS-CRC, resulting in a lower tumor mutation burden and reduced neoantigen configuration.…”

Section: Immune Profiling Of Msi and Mss Crc Influence Icis Successmentioning

confidence: 99%

Molecular insights into clinical trials for immune checkpoint inhibitors in colorectal cancer: Unravelling challenges and future directions

Sharma,

Singh,

Turk

et al. 2024

World J Gastroenterol

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Colorectal cancer (CRC) is a complex disease with diverse etiologies and clinical outcomes. Despite considerable progress in development of CRC therapeutics, challenges remain regarding the diagnosis and management of advanced stage metastatic CRC (mCRC). In particular, the five-year survival rate is very low since mCRC is currently rarely curable. Over the past decade, cancer treatment has significantly improved with the introduction of cancer immunotherapies, specifically immune checkpoint inhibitors. Therapies aimed at blocking immune checkpoints such as PD-1, PD-L1, and CTLA-4 target inhibitory pathways of the immune system, and thereby enhance anti-tumor immunity. These therapies thus have shown promising results in many clinical trials alone or in combination. The efficacy and safety of immunotherapy, either alone or in combination with CRC, have been investigated in several clinical trials. Clinical trials, including KEYNOTE-164 and CheckMate 142, have led to Food and Drug Administration approval of the PD-1 inhibitors pembrolizumab and nivolumab, respectively, for the treatment of patients with unresectable or metastatic microsatellite instability-high or deficient mismatch repair CRC. Unfortunately, these drugs benefit only a small percentage of patients, with the benefits of immunotherapy remaining elusive for the vast majority of CRC patients. To this end, primary and secondary resistance to immunotherapy remains a significant issue, and further research is necessary to optimize the use of immunotherapy in CRC and identify biomarkers to predict the response. This review provides a comprehensive overview of the clinical trials involving immune checkpoint inhibitors in CRC. The underlying rationale, challenges faced, and potential future steps to improve the prognosis and enhance the likelihood of successful trials in this field are discussed.

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