Camptothecin Induces PD-L1 and Immunomodulatory Cytokines in Colon Cancer Cells

Bedi, Deepa; Henderson, Henry J.; Manne, Upender; Samuel, Temesgen

doi:10.3390/medicines6020051

Cited by 26 publications

(23 citation statements)

References 32 publications

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“…Various studies have shown that elevated levels of CCL21/CCR7 lead to migration and proliferation of cancerous cells [ 47 , 48 ], although decreased expression of CCL21 was reported in human colorectal adenocarcinoma [ 49 ]. Downregulation of CCL21 is attributed to upregulated expression of SPP1 in cervical cancer tissue [ 50 ]. Further, we validated these DEGs by using the TCGA database.…”

Section: Discussionmentioning

confidence: 99%

Identification of Differentially Expressed Genes in Cervical Cancer Patients by Comparative Transcriptome Analysis

Annapurna

Pasumarthi

Pasha

et al. 2021

BioMed Research International

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Cervical cancer is one of the most malignant reproductive diseases seen in women worldwide. The identification of dysregulated genes in clinical samples of cervical cancer may pave the way for development of better prognostic markers and therapeutic targets. To identify the dysregulated genes (DEGs), we have retrospectively collected 10 biopsies, seven from cervical cancer patients and three from normal subjects who underwent a hysterectomy. Total RNA isolated from biopsies was subjected to microarray analysis using the human Clariom D Affymetrix platform. Based on the results of principal component analysis (PCA), only eight samples are qualified for further studies; GO and KEGG were used to identify the key genes and were compared with TCGA and GEO datasets. Identified genes were further validated by quantitative real-time PCR and receiver operating characteristic (ROC) curves, and the highest Youden index was calculated in order to evaluate cutoff points (COPs) that allowed distinguishing of tissue samples of cervical squamous carcinoma patients from those of healthy individuals. By comparative microarray analysis, a total of 108 genes common across the six patients’ samples were chosen; among these, 78 genes were upregulated and 26 genes were downregulated. The key genes identified were SPP1, LYN, ARRB2, COL6A3, FOXM1, CCL21, TTK, and MELK. Based on their relative expression, the genes were ordered as follows: TTK > ARRB2 > SPP1 > FOXM1 > LYN > MELK > CCL21 > COL6A3; this generated data is in sync with the TCGA datasets, except for ARRB2. Protein-protein interaction network analysis revealed that TTK and MELK are closely associated with SMC4, AURKA, PLK4, and KIF18A. The candidate genes SPP1, FOXM1, LYN, COL6A3, CCL21, TTK and MELK at mRNA level, emerge as promising candidate markers for cervical cancer prognosis and also emerge as potential therapeutic drug targets.

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Section: Discussionmentioning

confidence: 99%

Identification of Differentially Expressed Genes in Cervical Cancer Patients by Comparative Transcriptome Analysis

Annapurna

Pasumarthi

Pasha

et al. 2021

BioMed Research International

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“…Pre-clinical studies evaluating chemotherapy in combination with ICIs have shown that while favorable interactions can occur, effects depend on the tumor model, the type of chemotherapy and the ICI. Chemotherapy, including 5-FU [ 138 ], upregulated PD-L1 expression on CRC cells with the effects greatest for camptothecin [ 139 ]. The combination of capecitabine+oxaliplatin chemotherapy enhanced anti-PD1 ICI in an MC-38 CRC model [ 140 ].…”

Section: Modulation Of 5-fu-induced Anti-tumor Immunitymentioning

confidence: 99%

Fluoropyrimidine Modulation of the Anti-Tumor Immune Response―Prospects for Improved Colorectal Cancer Treatment

Gmeiner

2020

Cancers

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Chemotherapy modulates the anti-tumor immune response and outcomes depend on the balance of favorable and unfavorable effects of drugs on anti-tumor immunity. 5-Florouracil (5-FU) is widely used in adjuvant chemotherapy regimens to treat colorectal cancer (CRC) and provides a survival benefit. However, survival remains poor for CRC patients with advanced and metastatic disease and immune checkpoint blockade therapy benefits only a sub-set of CRC patients. Here we discuss the effects of 5-FU-based chemotherapy regimens to the anti-tumor immune response. We consider how different aspects of 5-FU’s multi-factorial mechanism differentially affect malignant and immune cell populations. We summarize recent studies with polymeric fluoropyrimidines (e.g., F10, CF10) that enhance DNA-directed effects and discuss how such approaches may be used to enhance the anti-tumor immune response and improve outcomes.

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“…Moreover, this analysis suggested that macrophages in EA tumors had a greater proportion with a M1 phenotype that is typically associated with a favorable immune response. Associated with poor outcome in study of topoisomerase inhibitors in CRC (36) Supplemental Fig. 1: Correlation between MHC class 1 molecules and immune markers.…”

Section: Clinical Crc Patient Characteristicsmentioning

confidence: 99%

Differential Immune Signatures in the Tumor Microenvironment are Associated with Colorectal Cancer Racial Disparities: A Cohort Study of Biorepository Data

Curran¹,

Sun²,

Gerry³

et al. 2020

Preprint

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Background: Disparities in colorectal cancer outcomes may be due to a more aggressive phenotype in African American patients in the setting of a decreased tumor immunity, though the precise mechanism for this result has not been well elucidated. To explore the molecular factors underlying colorectal cancer disparities, we compared the immunogenomic signatures of colorectal cancer from African American and European American patients.Methods: We identified all colorectal cancer patients from the publicly available Cancer Genome Atlas for whom race and survival data are available. Immunophenotype signatures were established for African American and European American patients. Comparisons were made regarding survival and a multivariable linear regression model was created to determine the association of immune cellular components with race. Differential gene expression was also assessed. Results: Of the 254 patients identified, 58 (23%) were African American and 196 (77%) were European American. African American patients had a decreased progression free survival (p=0.04). Tumors from African American patients displayed a reduced fraction of macrophages and CD8+ T cells and an increased fraction of B cells compared with tumors from European Americans. Differences persisted when controlling for sex, age and disease stage. Immunostimulatory and immunoinhibitory gene profiles including MHC expression differed by race. Conclusions: Differences in the tumor immune microenvironment of African American as compared to European American colorectal cancer specimens may play a role in the survival differences between the groups. These differences may provide targeted therapeutic opportunities.

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Camptothecin Induces PD-L1 and Immunomodulatory Cytokines in Colon Cancer Cells

Cited by 26 publications

References 32 publications

Identification of Differentially Expressed Genes in Cervical Cancer Patients by Comparative Transcriptome Analysis

Identification of Differentially Expressed Genes in Cervical Cancer Patients by Comparative Transcriptome Analysis

Fluoropyrimidine Modulation of the Anti-Tumor Immune Response―Prospects for Improved Colorectal Cancer Treatment

Differential Immune Signatures in the Tumor Microenvironment are Associated with Colorectal Cancer Racial Disparities: A Cohort Study of Biorepository Data

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