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

ABSTRACT: 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-?, programmed death-1, ?2-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.

SUBMITTER: Bakhrebah MA

PROVIDER: S-EPMC7658510 | biostudies-literature | 2020 Jan-Dec

REPOSITORIES: biostudies-literature

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

Bakhrebah Muhammed A MA Nasrullah Mohammad M Abdulaal Wesam H WH Hassan Mohammed A MA Siddiqui Halima H Al Doghaither Huda H Omar Ulfat M UM Helmi Nawal N Fallatah Mohannad M MM Al-Ghafari Ayat B AB Khan Mohammad Imran MI Choudhry Hani H

Technology in cancer research & treatment 20200101

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 ...[more]

PMID: 33153413

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Project description:BackgroundProgrammed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) blockade immunotherapies have changed the landscape of cancer therapy. However, the main limitation of these therapies is the lack of definitively predictive biomarkers to predict treatment response. Whether PD-L1 expression on circulating tumor cells (CTCs) is associated with the clinical outcomes of immunotherapy remains to be extensively investigated.Materials and methodsOne hundred fifty-five patients with different advanced cancers were enrolled in this study and treated with anti-PD-1/PD-L1 monoclonal antibodies. Using the Pep@MNPs method, CTCs were isolated and enumerated. The PD-L1 expression levels were analyzed by an immunofluorescence assay for semiquantitative assessment with four categories (negative, low, medium, and high).ResultsPrior to immunotherapy, 81.93% (127/155) of patients had PD-L1-positive CTCs, and 71.61% (111/155) had at least one PD-L1-high CTC. The group with PD-L1-positive CTCs had a higher disease control rate (DCR) (71.56%, 91/127), with a DCR of only 39.29% (11/28) for the remaining individuals (p = .001). The objective response rate and DCR in PD-L1-high patients were higher than those in the other patients (32.44% vs. 13.64%, p = .018 and 75.68% vs. 40.91%, p < .0001, respectively). The reduction in the counts and ratios of PD-L1-positive CTCs and PD-L1-high CTCs reflected a beneficial response to PD-1/PD-L1 inhibitors. Furthermore, patients with PD-L1-high CTCs had significantly longer progression-free survival (4.9 vs. 2.2 months, p < .0001) and overall survival (16.1 vs. 9.0 months, p = .0235) than those without PD-L1-high CTCs.ConclusionThe PD-L1 level on CTCs may serve as a clinically actionable biomarker for immunotherapy, and its dynamic changes could predict the therapeutic response.Implications for practiceThis study was designed to investigate the role of programmed death-ligand 1 (PD-L1) expression on circulating tumor cells in predicting and monitoring response to programmed death-1 (PD-1)/PD-L1 blockade immunotherapies in patients with advanced cancer. The results of the study showed that PD-L1-high-expression circulating tumor cells (CTCs) were both a predictive biomarker and a prognostic factor in patients with advanced cancer treated with anti-PD-1/PD-L1 monoclonal antibodies. These observations suggest that PD-L1 level on CTCs is a potential clinical biomarker for immunotherapy.

Dataset Information

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

Publications

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

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