scholarly journals The features of host immune response with respect to microsatellite status of colorectal cancer

2007 ◽  
Vol 15 (1-2) ◽  
pp. 5-9
Author(s):  
Attila Fenyvesi
Keyword(s):  
Colorectal Cancer ◽  
Immune Response ◽  
Immune Responses ◽  
Continuous Production ◽  
Tumor Infiltrating Lymphocytes ◽  
Host Immune Response ◽  
Genetic Alterations ◽  
Clinicopathological Characteristics ◽  
Melting Point Analysis ◽  
Peritumoral Stroma

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.

scholarly journals High Expression of Pd-1 in Circulating Cells of Patients With Advanced Colorectal Cancer Receiving Adjuvant Therapy

2020 ◽  
Vol 19 ◽  
pp. 153303382096944
Author(s):  
Muhammed A. Bakhrebah ◽  
Mohammad Nasrullah ◽  
Wesam H. Abdulaal ◽  
Mohammed A. Hassan ◽  
Halima Siddiqui ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Immune Response ◽  
Adjuvant Therapy ◽  
Tumor Cells ◽  
Immune Cells ◽  
Human Leukocyte ◽  
Genetic Alterations ◽  
Programmed Death ◽  
Programmed Death 1 ◽  
Cancer Types

Among all cancer types, colorectal cancer is the third most common in men and the second most common in women globally. Generally, the risk of colorectal cancer increases with age, and colorectal cancer is modulated by various genetic alterations. Alterations in the immune response serve a significant role in the development of colorectal cancer. In primary cancer types, immune cells express a variety of inhibitory molecules that dampen the immune response against tumor cells. Additionally, few reports have demonstrated that classical chemotherapy promotes the immunosuppressive microenvironment in both tissues and immune cells. This study assessed the expression levels of genes using RT-qPCR associated with the immune system, including interferon-γ, programmed death-1, β2-microglobulin, human leukocyte antigen-A, CD3e, CD28 and intracellular adhesion molecule 1, in patients with colorectal cancer, as these genes are known to serve important roles in immune regulation during cancer incidence. Gene expression analysis was performed with the whole blood cells of patients with colorectal cancer and healthy volunteers. Compared with the normal controls, programmed death-1was highly expressed in patients with advanced-stage colorectal cancer. Furthermore, the expression of programmed death-1 was higher in patients receiving adjuvant therapy, which suggests the therapy dampened the immune response against tumor cells. The results of the present study indicate that classical adjuvant therapies, which are currently used for patients with colorectal cancer, should be modulated, and a combination of classical therapy with anti-programmed death-1 antibody should be conducted for improved management of patients with colorectal cancer.

scholarly journals DNA methylation-based signature of CD8+ tumor-infiltrating lymphocytes enables evaluation of immune response and prognosis in colorectal cancer

2021 ◽  
Vol 9 (9) ◽  
pp. e002671
Author(s):  
Qi Zou ◽  
Xiaolin Wang ◽  
Donglin Ren ◽  
Bang Hu ◽  
Guannan Tang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Dna Methylation ◽  
Immune Response ◽  
T Cell ◽  
Strong Association ◽  
Tumor Infiltrating Lymphocytes ◽  
Cd8 T Cell ◽  
Therapeutic Approaches ◽  
Single Base Resolution ◽  
Infiltrating Lymphocytes

BackgroundTumor-infiltrating lymphocytes (TILs), especially CD8+ TILs, can be used for predicting immunotherapy responsiveness and survival outcome. However, the evaluation of CD8+ TILs currently relies on histopathological methodology with high variability. We therefore aimed to develop a DNA methylation signature for CD8+ TILs (CD8+ MeTIL) that could evaluate immune response and prognosis in colorectal cancer (CRC).MethodsA CD8+ MeTIL signature score was constructed by using CD8+ T cell-specific differentially methylated positions (DMPs) that were identified from Illumina EPIC methylation arrays. Immune cells, colon epithelial cells, and two CRC cohorts (n=282 and 335) were used to develop a PCR-based assay for quantitative analysis of DNA methylation at single-base resolution (QASM) to determine CD8 + MeTIL signature score.ResultsThree CD8+ T cell-specific DMPs were identified to construct the CD8+ MeTIL signature score, which showed a dramatic discriminability between CD8+ T cells and other cells. The QASM assay we developed for CD8+ MeTIL markers could measure CD8+ TILs distributions in a fully quantitative, accurate, and simple manner. The CD8+ MeTIL score determined by QASM assay showed a strong association with histopathology-based CD8+ TIL counts and a gene expression-based immune marker. Furthermore, the low CD8+ MeTIL score (enriched CD8+ TILs) was associated with MSI-H tumors and predicted better survival in CRC cohorts.ConclusionsThis study developed a quantitative DNA methylation-based signature that was reliable to evaluate CD8+ TILs and prognosis in CRC. This approach has the potential to be a tool for investigations on CD8+ TILs and a biomarker for therapeutic approaches, including immunotherapy.

scholarly journals mSphere of Influence: Role of IRGM1 in Disease Control

mSphere ◽  
2021 ◽  
Vol 6 (2) ◽  
Author(s):  
Sumanta Kumar Naik
Keyword(s):  
Immune Response ◽  
Quality Control ◽  
Mycobacterium Tuberculosis ◽  
Immune Responses ◽  
Disease Control ◽  
Host Immune Response ◽  
Specific Interest ◽  
Mitochondrial Quality Control ◽  
Content Type

ABSTRACT Sumanta K. Naik works in the tuberculosis field, with a specific interest in the host immune response to Mycobacterium tuberculosis infection. In this mSphere of Influence article, he reflects on how the paper “IRGM1 links mitochondrial quality control to autoimmunity” by Prashant Rai et al. (Nat Immunol, 22:312–321, 2021, https://doi.org/10.1038/s41590-020-00859-0) impacted his research by revealing new roles for Irgm1 in immune responses.

scholarly journals Remodelling of colorectal cancer cell signaling by microbiota and immunity in diabetes

2021 ◽  
Author(s):  
María Gutiérrez-Salmerón ◽  
Silvia Rocío Rocío Lucena ◽  
Ana Chocarro-Calvo ◽  
Jose Manuel Garcia-Martinez ◽  
Rosa M Martín Orozco ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Immune Response ◽  
Immune Responses ◽  
Inflammatory Cells ◽  
Low Grade ◽  
Gut Barrier ◽  
Anti Inflammatory ◽  
And Migration ◽  
Factor Α ◽  
And Function

Obesity is the strongest known risk factor to develop Type 2 diabetes (T2D) and both share a state of chronic, diffuse and low-grade inflammation, impaired immune responses and alterations in the composition and function of the microbiome. Notably, these hallmarks are shared with colorectal cancer (CRC), which is epidemiologically associated to obesity and T2D. Gut barrier damages in T2D, destabilize the microbiome that metabolizes the diet and modulates the host immune response triggering inflammatory and proliferative pathways. In this review, we discuss the pathways altered by defects in the immune response and microbiota that may link T2D to CRC development. Stressed adipocytes, metabolic incongruity in blood and gut barrier failure with dysbiosis cooperate to establish imbalances between immune innate and adaptive cells and cytokines such as interleukin 6 (IL-6) or tumour necrosis factor α (TNF-α) that define low-grade diffuse inflammation in T2D. Inflammation drives tissue repair through proliferation and migration (critical mechanisms for tumourigenesis) and under physiological conditions feeds anti-inflammatory cytokine production to resolve the process. The disproportion in pro- versus anti-inflammatory cells and cytokines imposed by T2D will impact the tumour micro- and macro-environment, favouring tumour proliferation, angiogenesis and decreased immune responses. Complex bidirectional relationships between the metabolic environment of T2D, gut microbiota, and immune dysfunctions may favour tumour cell demands and will define the outcome. Animal models developed to study the relationships between T2D and CRC in the context of microbiota and immune system are discussed.

scholarly journals Impact of Toll-Like Receptor-Specific Agonists on the Host Immune Response to the Yersinia pestis Plague rF1V Vaccine

2021 ◽  
Vol 12 ◽  
Author(s):  
Sergei Biryukov ◽  
Jennifer L. Dankmeyer ◽  
Zain Shamsuddin ◽  
Ivan Velez ◽  
Nathaniel O. Rill ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Fusion Protein ◽  
Yersinia Pestis ◽  
Vaccine Efficacy ◽  
Host Immune Response ◽  
Toll Like Receptor ◽  
Vaccine Strategy ◽  
Pneumonic Plague ◽  
Plague Vaccine

Relatively recent advances in plague vaccinology have produced the recombinant fusion protein F1-V plague vaccine. This vaccine has been shown to readily protect mice from both bubonic and pneumonic plague. The protection afforded by this vaccine is solely based upon the immune response elicited by the F1 or V epitopes expressed on the F1-V fusion protein. Accordingly, questions remain surrounding its efficacy against infection with non-encapsulated (F1-negative) strains. In an attempt to further optimize the F1-V elicited immune response and address efficacy concerns, we examined the inclusion of multiple toll-like receptor agonists into vaccine regimens. We examined the resulting immune responses and also any protection afforded to mice that were exposed to aerosolized Yersinia pestis. Our data demonstrate that it is possible to further augment the F1-V vaccine strategy in order to optimize and augment vaccine efficacy.

Understanding the immune responses involved in mediating protection or immunopathology during leishmaniasis

2021 ◽  
Author(s):  
Thalia Pacheco-Fernandez ◽  
Greta Volpedo ◽  
Chaitenya Verma ◽  
Abhay R. Satoskar
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Public Health Problem ◽  
Host Immune Response ◽  
Sand Fly ◽  
Leishmania Infection ◽  
Major Public Health Problem ◽  
Wide Range ◽  
Vector Borne ◽  
Leishmania Parasites

Leishmaniasis is a vector-borne Neglected Tropical Disease (NTD) transmitted by the sand fly and is a major public health problem worldwide. Infections caused by Leishmania clinically manifest as a wide range of diseases, such as cutaneous (CL), diffuse cutaneous (DCL), mucosal (MCL) and visceral leishmaniasis (VL). The host innate and adaptative immune responses play critical roles in the defense against leishmaniasis. However, Leishmania parasites also manipulate the host immune response for their survival and replication. In addition, other factors such as sand fly salivary proteins and microbiota also promote disease susceptibility and parasite spread by modulating local immune response. Thus, a complex interplay between parasite, sand fly and the host immunity governs disease severity and outcome. In this review, we discuss the host immune response during Leishmania infection and highlight the factors associated with resistance or susceptibility.

scholarly journals Clone-specific immune reactions in a trematode-crustacean system

Parasitology ◽  
2011 ◽  
Vol 139 (1) ◽  
pp. 128-136 ◽  
Author(s):  
ANSON V. KOEHLER ◽  
ROBERT POULIN
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Microsatellite Markers ◽  
Immune Reaction ◽  
Host Immune Response ◽  
Ecological Immunology ◽  
Experimental Exposure ◽  
Immune Reactions ◽  
Essential Aspect

SUMMARYVariability of immune responses is an essential aspect of ecological immunology, yet how much of this variability is due to differences among parasite genotypes remains unknown. Here, variation in immune response of the crab, Macrophthalmus hirtipes, is examined as a function of experimental exposure to 10 clonal cercarial lineages of the trematode Maritrema novaezealandensis. Our goals were (1) to assess the variability of the host immune reaction elicited by 10 parasite clones, (2) to test if the heterozygosity–fitness correlation, whereby organisms with higher heterozygosities achieve a higher fitness than those with lower heterozygosities, applies to heterozygous parasites eliciting weak immune responses, and (3) to see how concomitant infections by other macroparasites influence the crab's immune response to cercariae. Parasite clones were distinguished and heterozygosities calculated using 20 microsatellite markers. We found that exposure to cercariae resulted in increased haemocyte counts, and that although interclonal differences in immune response elicited were detected, parasite heterozygosity did not correlate with host immune response. Additionally, the presence of other pre-existing parasites in hosts did not influence their immune response following experimental exposure to cercariae. Overall, the existence of variability in immune response elicited by different parasite clones is promising for future ecological immunology studies using this system.

Sign in / Sign up

Export Citation Format

Share Document