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      Inflammatory Markers in Cancer Immunotherapy

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          Abstract

          Simple Summary

          Inflammation has been recognized to be linked to tumor development. Several markers of inflammation can be detected via blood such as variety of blood cells, which can be readily and easily obtained. These markers have been studied as ways to predict and prognosticate tumor response to chemotherapy. With the development of immunotherapy, namely immune checkpoint inhibitors (ICIs) such as cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed cell death protein 1 (PD-1), and programmed death ligand 1 (PDL-1) PDL-1 inhibitors, several markers have also been studied in assessing tumor response. In this review, we will discuss the various inflammatory markers that have been studied in several tumors treated with ICIs.

          Abstract

          Chronic inflammation is considered a major risk factor for cancer formation. Inflammation within the tumor environment plays a role in its response to therapy, growth, and prognosis. Cancer associated inflammation is known to occur in the tumor microenvironment and in the systemic circulation, and is correlated with disease progression and prognosis in many cancers. Blood cells such as neutrophils, lymphocytes, platelets, and circulating proteins such as C-reactive protein, and interleukins, such as IL-6, have been associated with inflammatory responses, which contribute to tumorigenesis. Cancer has found ways to evade the immune response; a pathway that can attenuate the innate immune response is via blocking immune checkpoints. Development of monoclonal antibodies against inhibitory immune checkpoints such as cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1) have given rise to immunotherapy, which has shown remarkable responses in anti-tumor activity resulting in several U.S. Federal and Drug Administration (FDA)-approved checkpoint inhibitors. Various inflammatory markers and their prognostic and predictive implications in malignancies treated with immunotherapy will be discussed in this review.

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          Most cited references73

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          Improved Survival with Ipilimumab in Patients with Metastatic Melanoma

          An improvement in overall survival among patients with metastatic melanoma has been an elusive goal. In this phase 3 study, ipilimumab--which blocks cytotoxic T-lymphocyte-associated antigen 4 to potentiate an antitumor T-cell response--administered with or without a glycoprotein 100 (gp100) peptide vaccine was compared with gp100 alone in patients with previously treated metastatic melanoma. A total of 676 HLA-A*0201-positive patients with unresectable stage III or IV melanoma, whose disease had progressed while they were receiving therapy for metastatic disease, were randomly assigned, in a 3:1:1 ratio, to receive ipilimumab plus gp100 (403 patients), ipilimumab alone (137), or gp100 alone (136). Ipilimumab, at a dose of 3 mg per kilogram of body weight, was administered with or without gp100 every 3 weeks for up to four treatments (induction). Eligible patients could receive reinduction therapy. The primary end point was overall survival. The median overall survival was 10.0 months among patients receiving ipilimumab plus gp100, as compared with 6.4 months among patients receiving gp100 alone (hazard ratio for death, 0.68; P<0.001). The median overall survival with ipilimumab alone was 10.1 months (hazard ratio for death in the comparison with gp100 alone, 0.66; P=0.003). No difference in overall survival was detected between the ipilimumab groups (hazard ratio with ipilimumab plus gp100, 1.04; P=0.76). Grade 3 or 4 immune-related adverse events occurred in 10 to 15% of patients treated with ipilimumab and in 3% treated with gp100 alone. There were 14 deaths related to the study drugs (2.1%), and 7 were associated with immune-related adverse events. Ipilimumab, with or without a gp100 peptide vaccine, as compared with gp100 alone, improved overall survival in patients with previously treated metastatic melanoma. Adverse events can be severe, long-lasting, or both, but most are reversible with appropriate treatment. (Funded by Medarex and Bristol-Myers Squibb; ClinicalTrials.gov number, NCT00094653.)
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            Inflammation and cancer.

            Recent data have expanded the concept that inflammation is a critical component of tumour progression. Many cancers arise from sites of infection, chronic irritation and inflammation. It is now becoming clear that the tumour microenvironment, which is largely orchestrated by inflammatory cells, is an indispensable participant in the neoplastic process, fostering proliferation, survival and migration. In addition, tumour cells have co-opted some of the signalling molecules of the innate immune system, such as selectins, chemokines and their receptors for invasion, migration and metastasis. These insights are fostering new anti-inflammatory therapeutic approaches to cancer development.
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              Immunity, inflammation, and cancer.

              Inflammatory responses play decisive roles at different stages of tumor development, including initiation, promotion, malignant conversion, invasion, and metastasis. Inflammation also affects immune surveillance and responses to therapy. Immune cells that infiltrate tumors engage in an extensive and dynamic crosstalk with cancer cells, and some of the molecular events that mediate this dialog have been revealed. This review outlines the principal mechanisms that govern the effects of inflammation and immunity on tumor development and discusses attractive new targets for cancer therapy and prevention. 2010 Elsevier Inc. All rights reserved.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Biology (Basel)
                Biology (Basel)
                biology
                Biology
                MDPI
                2079-7737
                13 April 2021
                April 2021
                : 10
                : 4
                : 325
                Affiliations
                [1 ]Department of Hematology and Medical Oncology, Winship Cancer Institute of Emory University, Atlanta, GA 30322, USA; dravind@ 123456emory.edu
                [2 ]Department of Urology, Emory University School of Medicine, Atlanta, GA 30322, USA; vmaster@ 123456emory.edu
                Author notes
                [* ]Correspondence: mehmet.a.bilen@ 123456emory.edu ; Tel.: +1-404-778-3693
                Author information
                https://orcid.org/0000-0003-0364-9027
                Article
                biology-10-00325
                10.3390/biology10040325
                8069970
                33924623
                6149b1a4-91d2-410c-b603-ff6e5d19a314
                © 2021 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( https://creativecommons.org/licenses/by/4.0/).

                History
                : 14 March 2021
                : 10 April 2021
                Categories
                Review

                immunotherapy,inflammation,pd-1 inhibitors,pdl-1 inhibitors,ctla-4 monoclonal antibodies,neutrophil-lymphocyte ratio,platelet-lymphocyte ratio,lymphocyte-monocyte ratio

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