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      Pan-immune-inflammation Value and Prognosis in Patients With Esophageal Cancer

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          Abstract

          Supplemental Digital Content is available in the text.

          Abstract

          Mini-abstract:

          The pan-immune-inflammation value was associated with clinical outcomes and tumor-infiltrating lymphocytes in 866 esophageal cancers. Systemic immune competence may influence patient prognosis through local immune response.

          Objective:

          To examine the relationship between the pan-immune-inflammation value (PIV), tumor immunity, and clinical outcomes in 866 patients with esophageal cancer.

          Background:

          The PIV, calculated from all immune-inflammatory cells in the peripheral blood count, is a recently proposed marker for clinical outcomes in some types of cancers. Nonetheless, the prognostic significance of PIV in esophageal cancer remains unclear.

          Methods:

          In the derivation cohort (n = 433), we set the optimal cutoff value using a time-dependent receiver operating characteristic (ROC) curve. In the validation cohort (n = 433), the relationships between the PIV, tumor-infiltrating lymphocytes (TILs), CD8 expression by immunohistochemical staining, and patient prognosis were examined.

          Results:

          The area under the ROC curve for the PIV at 5 years was 0.631 in the derivation cohort. The validation cohort, divided into PIV-low cases (n = 223) and PIV-high cases (n = 210), showed significantly worse overall survival (log-rank P = 0.0065; hazard ratio [HR]: 1.48; 95% confidence interval [CI]: 1.12–1.98; P < 0.001; multivariate HR: 1.41; 95% CI: 1.05–1.90; P = 0.023). The prognostic effect of the PIV was not significantly modified by any clinical characteristics ( P for interaction > 0.05). The PIV-high cases were significantly associated with a low TIL status ( P < 0.001) and low CD8-positive cell counts ( P = 0.011).

          Conclusions:

          The PIV was associated with clinical outcomes in esophageal cancer, supporting its role as a prognostic biomarker. Considering the relationship between the PIV and TILs, systemic immune competence may influence patient prognosis through a local immune response.

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          Global Cancer Statistics 2018: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries

          Ahmedin Jemal, Lindsey A Torre, Rebecca Siegel … (2018)
          This article provides a status report on the global burden of cancer worldwide using the GLOBOCAN 2018 estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer, with a focus on geographic variability across 20 world regions. There will be an estimated 18.1 million new cancer cases (17.0 million excluding nonmelanoma skin cancer) and 9.6 million cancer deaths (9.5 million excluding nonmelanoma skin cancer) in 2018. In both sexes combined, lung cancer is the most commonly diagnosed cancer (11.6% of the total cases) and the leading cause of cancer death (18.4% of the total cancer deaths), closely followed by female breast cancer (11.6%), prostate cancer (7.1%), and colorectal cancer (6.1%) for incidence and colorectal cancer (9.2%), stomach cancer (8.2%), and liver cancer (8.2%) for mortality. Lung cancer is the most frequent cancer and the leading cause of cancer death among males, followed by prostate and colorectal cancer (for incidence) and liver and stomach cancer (for mortality). Among females, breast cancer is the most commonly diagnosed cancer and the leading cause of cancer death, followed by colorectal and lung cancer (for incidence), and vice versa (for mortality); cervical cancer ranks fourth for both incidence and mortality. The most frequently diagnosed cancer and the leading cause of cancer death, however, substantially vary across countries and within each country depending on the degree of economic development and associated social and life style factors. It is noteworthy that high-quality cancer registry data, the basis for planning and implementing evidence-based cancer control programs, are not available in most low- and middle-income countries. The Global Initiative for Cancer Registry Development is an international partnership that supports better estimation, as well as the collection and use of local data, to prioritize and evaluate national cancer control efforts. CA: A Cancer Journal for Clinicians 2018;0:1-31. © 2018 American Cancer Society.
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            Cancer immunotherapy using checkpoint blockade

            Jedd Wolchok, Antoni Ribas (2018)
            The release of negative regulators of immune activation (immune checkpoints) that limit antitumor responses has resulted in unprecedented rates of long-lasting tumor responses in patients with a variety of cancers. This can be achieved by antibodies blocking the cytotoxic T lymphocyte antigen-4 (CTLA-4) or the programmed death-1 (PD-1) pathway, either alone or in combination. The main premise for inducing an immune response is the pre-existence of antitumor T cells that were limited by specific immune checkpoints. Most patients who have tumor responses maintain long lasting disease control, yet one third of patients relapse. Mechanisms of acquired resistance are currently poorly understood, but evidence points to alterations that converge on the antigen presentation and interferon gamma signaling pathways. New generation combinatorial therapies may overcome resistance mechanisms to immune checkpoint therapy.
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              PD-1 blockade induces responses by inhibiting adaptive immune resistance

              Paul Tumeh, Christina L. Harview, Jennifer Yearley … (2014)
              Therapies that target the programmed death-1 (PD-1) receptor have shown unprecedented rates of durable clinical responses in patients with various cancer types. 1–5 One mechanism by which cancer tissues limit the host immune response is via upregulation of PD-1 ligand (PD-L1) and its ligation to PD-1 on antigen-specific CD8 T-cells (termed adaptive immune resistance). 6,7 Here we show that pre-existing CD8 T-cells distinctly located at the invasive tumour margin are associated with expression of the PD-1/PD-L1 immune inhibitory axis and may predict response to therapy. We analyzed samples from 46 patients with metastatic melanoma obtained before and during anti-PD1 therapy (pembrolizumab) using quantitative immunohistochemistry, quantitative multiplex immunofluorescence, and next generation sequencing for T-cell receptors (TCR). In serially sampled tumours, responding patients showed proliferation of intratumoural CD8+ T-cells that directly correlated with radiographic reduction in tumour size. Pre-treatment samples obtained from responding patients showed higher numbers of CD8, PD1, and PD-L1 expressing cells at the invasive tumour margin and inside tumours, with close proximity between PD-1 and PD-L1, and a more clonal TCR repertoire. Using multivariate analysis, we established a predictive model based on CD8 expression at the invasive margin and validated the model in an independent cohort of 15 patients. Our findings indicate that tumour regression following therapeutic PD-1 blockade requires pre-existing CD8+ T cells that are negatively regulated by PD-1/PD-L1 mediated adaptive immune resistance.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Ann Surg Open
                Journal ID (iso-abbrev): Ann Surg Open
                Journal ID (publisher-id): AS9
                Title: Annals of Surgery Open
                Publisher: Wolters Kluwer Health, Inc. (Two Commerce Square, 2001 Market Street, Philadelphia, PA 19103 )
                ISSN (Electronic): 2691-3593
                Publication date Collection: March 2022
                Publication date (Electronic): 22 December 2021
                Volume: 3
                Issue: 1
                Electronic Location Identifier: e113
                Affiliations
                From the [* ]Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
                [† ]Department of Next-Generation Surgical Therapy Development, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
                Author notes
                Reprints: Hideo Baba, MD, PhD, FACS, Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto 860-8556, Japan. E-mail: hdobaba@ 123456kumamoto-u.ac.jp .
                Article
                Accession ID: 00002
                DOI: 10.1097/AS9.0000000000000113
                PMC ID: 10431581
                PubMed ID: 37600089
                SO-VID: 1c353f08-659e-45d9-8851-bd232a76f49f
                Copyright © Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc.
                License:

                This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

                History
                Date received : 20 September 2021
                Date accepted : 11 November 2021
                Categories
                Subject: Original Study
                Custom metadata
                OPEN-ACCESS TRUE
                SDC T

                Keywords: pan-immune-inflammation value,tumor-infiltrating lymphocytes,prognosis,esophageal cancer,tumor immunity
                Data availability:
                Keywords: pan-immune-inflammation value, tumor-infiltrating lymphocytes, prognosis, esophageal cancer, tumor immunity

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