Immune Cells in Colorectal Cancer: Prognostic Relevance and Role of MSI

Patients with inflammatory bowel disease (IBD) have increased incidence of colorectal cancer (CRC). IBD-associated cancer follows a well-characterized sequence of intestinal epithelial changes, in which genetic mutations and molecular aberrations play a key role. IBD-associated cancer develops against a background of chronic inflammation and pro-inflammatory immune cells, and their products contribute to cancer development and progression. In recent years, the effect of the immunosuppressive microenvironment in cancer development and progression has gained more attention, mainly because of the unprecedented anti-tumor effects of immune checkpoint inhibitors in selected groups of patients. Even though IBD-associated cancer develops in the background of chronic inflammation which is associated with activation of endogenous anti-inflammatory or suppressive mechanisms, the potential role of an immunosuppressive microenvironment in these cancers is largely unknown. In this review, we outline the role of the immune system in promoting cancer development in chronic inflammatory diseases such as IBD, with a specific focus on the anti-inflammatory mechanisms and suppressive immune cells that may play a role in IBD-associated tumorigenesis.

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Exploring the Inflammatory Pathogenesis of Colorectal Cancer

Diseases ◽

10.3390/diseases9040079 ◽

2021 ◽

Vol 9 (4) ◽

pp. 79

Author(s):

Ahamed A Khalyfa ◽

Shil Punatar ◽

Rida Aslam ◽

Alex Yarbrough

Keyword(s):

Colorectal Cancer ◽

Immune Cells ◽

Metabolic Pathways ◽

Genetic Alterations ◽

Chromosomal Damage ◽

Immune Mediators ◽

Growing Body ◽

Traditional Risk Factors ◽

Novel Associations

Colorectal cancer is one of the most commonly diagnosed cancers worldwide. Traditionally, mechanisms of colorectal cancer formation have focused on genetic alterations including chromosomal damage and microsatellite instability. In recent years, there has been a growing body of evidence supporting the role of inflammation in colorectal cancer formation. Multiple cytokines, immune cells such T cells and macrophages, and other immune mediators have been identified in pathways leading to the initiation, growth, and metastasis of colorectal cancer. Outside the previously explored mechanisms and pathways leading to colorectal cancer, initiatives have been shifted to further study the role of inflammation in pathogenesis. Inflammatory pathways have also been linked to some traditional risk factors of colorectal cancer such as obesity, smoking and diabetes, as well as more novel associations such as the gut microbiome, the gut mycobiome and exosomes. In this review, we will explore the roles of obesity and diet, smoking, diabetes, the microbiome, the mycobiome and exosomes in colorectal cancer, with a specific focus on the underlying inflammatory and metabolic pathways involved. We will also investigate how the study of colon cancer from an inflammatory background not only creates a more holistic and inclusive understanding of this disease, but also creates unique opportunities for prevention, early diagnosis and therapy.

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The role of inflammation in pathogenesis and treatment of colorectal cancer

Research n Practical Medicine Journal ◽

10.17709/2409-2231-2018-5-4-4 ◽

2018 ◽

Vol 5 (4) ◽

pp. 36-45

Author(s):

T. N. Garmanova ◽

M. I. Bredikhin ◽

I. A. Tulina ◽

P. V. Tsarkov

Keyword(s):

Colorectal Cancer ◽

Surgical Treatment ◽

Immune Cells ◽

Tumor Recurrence ◽

Surgical Intervention ◽

Factors Affecting ◽

Inflammatory Status ◽

Before And After ◽

The Impact

One of the factors affecting the effectiveness of treatment and determining the prognosis of a patient with colorectal cancer may be inflammatory status both before and after surgical treatment. The review is devoted to the description of possible mechanisms of relationa between patient's inflammatory status and oncogenesis. Particular attention is paid to the ability of tumor cells to modify the immune cells from the antioncogenic to prooncogenic status. The paper makes an attempt to present a unified concept of the impact of postoperative complications on tumor recurrence in the light of the inflammatory response to surgical intervention.

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Clinicopathological significance and prognostic role of tumor-infiltrating lymphocytes in colorectal cancer

The International Journal of Biological Markers ◽

10.1177/1724600818817320 ◽

2019 ◽

Vol 34 (2) ◽

pp. 132-138 ◽

Cited By ~ 9

Author(s):

Young San Ko ◽

Jung-Soo Pyo

Keyword(s):

Colorectal Cancer ◽

Immune Cells ◽

Tumor Infiltrating Lymphocytes ◽

Prognostic Role ◽

Significant Difference ◽

Clinicopathological Significance ◽

Cancer Tissues ◽

Infiltrating Lymphocytes ◽

The Impact

Purpose: This study aimed to elucidate the clinicopathological significance and prognostic role of tumor-infiltrating lymphocytes in colorectal cancer. Methods: The immunohistochemistry of CD3 and CD8 was performed on 265 human colorectal cancer tissues to investigate the tumor-infiltrating lymphocytes using Immunoscore. The correlation between Immunoscore and clinicopathological characteristics, including survival rates, was elucidated. In addition, the impact of tumor-infiltrating lymphocytes on programmed death-ligand 1 (PD-L1) protein expression was evaluated through immunohistochemistry. Results: Of the 265 colorectal cancer tissues, 40.8% had high Immunoscore, while 59.2% had low Immunoscore. A high Immunoscore was significantly correlated with favorable tumor behaviors, including lower rates of vascular, lymphatic, and perineural invasion; lymph node metastasis; and distant metastasis. PD-L1 expressions of tumor and immune cells were significantly higher in patients with high Immunoscore than in those with low Immunoscore. In addition, colorectal cancer tissues with high CD8-positive lymphocytes showed higher PD-L1 expressions of tumor and immune cells than colorectal cancer tissues with low CD8-positive lymphocytes. There was a significant correlation between high Immunoscore and better overall survival. However, there was no significant difference in survival rate according to PD-L1 expressions of tumor and immune cells in high and low Immunoscore subgroups. Conclusions: Taken together, our results showed that high tumor-infiltrating lymphocytes were significantly correlated with favorable tumor behaviors and better survival. In addition, there was a significant correlation between PD-L1 expression and tumor-infiltrating lymphocytes.

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The role of the organic anion transporting polypeptide OATP4A1 in immunactivation in colorectal cancer and inflammatory colon disease.

Journal of Clinical Oncology ◽

10.1200/jco.2014.32.3_suppl.481 ◽

2014 ◽

Vol 32 (3_suppl) ◽

pp. 481-481

Author(s):

Christoph Alexander Ausch ◽

Simone Zotter ◽

Maidah Scheikh ◽

Heike Bauer ◽

Marina Mollik ◽

...

Keyword(s):

Colorectal Cancer ◽

Cancer Cells ◽

Cancer Progression ◽

Immune Cells ◽

Immune Cell ◽

Organic Anion ◽

Staining Intensity ◽

Image Analysis System ◽

Cellular Markers

481 Background: OATP-transporter proteins, such as OATP4A1, present influence cancer progression by providing compounds (hormones, prostaglandins, cyclic nucleotides, second messenger proteins, drugs) which either inhibit or stimulate tumor cells growth. Therefore, OATP expression in cancer cells and in the stroma, i.e., the microenvironment surrounding the epithelial cells can become a critical parameter. Methods: OATP4A1 was investigated in paraffin-embedded specimens from 148 patients with colorectal cancer and 20 with diverticulitis by immunohistochemistry (IHC) on an automatic quantitative microscopic image analysis system (TissuesFaxs). With the Histoquest program, the immunoreactive score (IRS), was calculated from the degree of the staining intensity and the number of OATP4A1-positive cells. To identify OATP4A1+-cells, double-immunofluorescence staining (IF) was done with antibodies against appropriate cellular markers. Results: OATP4A1 was located in the membrane and cytosol of colon cancer cells and immune cells, while membranous OATP4A1staining was seen in normal mucosa. OATP4A1 levels were higher in cancer cells in patients without tumor recurrence for up to 5 years (NR) than in patients with an early relapse (R) having IRS of 4391±231 and 3026±373 (Mean±SEM), respectively. Highest OATP4A1 levels were observed in immune cells in the tumors of Rs (IRS, 5712 ±254, while in NRs they were lower (IRS: 3549±358; p=0.05). In both groups, OATP4A1 levels in stroma cells were low (288±54 vs. 611±82). OATP4A1 expressing immune cell subtypes in cancer and diverticulitis sections were identified as CD45+ leukocytes, CD3+ T- and CD20+ B-cells, CD68+ macrophages, CD34+precursor cells. OATP4A1 was not detectable in Conclusions: High levels of OATP4A1 in immune cells in malignant and non-malignant colon disease suggest a role of the transporter in the activation of the immune system in malignant and non-malignant colon disease. Whether OATP4A1 might be a therapeutical target has to be established.

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Immune cells in colorectal cancer: prognostic relevance and therapeutic strategies

Expert Review of Anticancer Therapy ◽

10.1586/14737140.8.4.561 ◽

2008 ◽

Vol 8 (4) ◽

pp. 561-572 ◽

Cited By ~ 58

Author(s):

Imke Atreya ◽

Markus F Neurath

Keyword(s):

Colorectal Cancer ◽

Immune Cells ◽

Therapeutic Strategies ◽

Prognostic Relevance

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The Contemporary Role of Resection and Ablation in Colorectal Cancer Liver Metastases

Digestive Disease Interventions ◽

10.1055/s-0040-1715816 ◽

2020 ◽

Vol 04 (03) ◽

pp. 291-302

Author(s):

Mariam F. Eskander ◽

Christopher T. Aquina ◽

Aslam Ejaz ◽

Timothy M. Pawlik

Keyword(s):

Colorectal Cancer ◽

Portal Vein ◽

Surgical Oncology ◽

Portal Vein Ligation ◽

Safe Alternative ◽

Colorectal Cancer Liver Metastases ◽

Liver Remnant ◽

New Era ◽

Ablation Therapy

AbstractAdvances in the field of surgical oncology have turned metastatic colorectal cancer of the liver from a lethal disease to a chronic disease and have ushered in a new era of multimodal therapy for this challenging illness. A better understanding of tumor behavior and more effective systemic therapy have led to the increased use of neoadjuvant therapy. Surgical resection remains the gold standard for treatment but without the size, distribution, and margin restrictions of the past. Lesions are considered resectable if they can safely be removed with tumor-free margins and a sufficient liver remnant. Minimally invasive liver resections are a safe alternative to open surgery and may offer some advantages. Techniques such as portal vein embolization, association of liver partition with portal vein ligation for staged hepatectomy, and radioembolization can be used to grow the liver remnant and allow for resection. If resection is not possible, nonresectional ablation therapy, including radiofrequency and microwave ablation, can be performed alone or in conjunction with resection. This article presents the most up-to-date literature on resection and ablation, with a discussion of current controversies and future directions.

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