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      Cytoreductive Nephrectomy Promoted Abscopal Effect of Camrelizumab Combined With Radiotherapy for Metastatic Renal Cell Carcinoma: A Case Report and Review of the Literature

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          Abstract

          There is little evidence around Camrelizumab combined with cytoreductive nephrectomy (CN) and radiotherapy (RT) as a treatment option for metastatic renal cell carcinoma (mRCC). The influence of CN on immune responses and the abscopal effect are not well understood. In this paper, we report a case of anti-programmed cell death-1 (PD-1) treated with combined RT once CN reduced the primary tumor burden (TB). This patient also encountered an increased response to targeted radiotherapy after immune resistance. We also observed a macrophage-to-lymphocyte ratio (MLR) peak, which may be correlated with subsequent pseudoprogression after thoracic radiotherapy. Consequently, even with the disease, this patient has remained stable. This peculiar instance suggests there is a need to investigate the underlying mechanisms of CN in promoting the abscopal effect during immunotherapy when combined with RT. It also suggests that there is a need for further investigation into the role of RT in overcoming immune resistance, and the value of MLR in predicting pseudoprogression. We hypothesize that a heavy tumor burden might suppress the abscopal effect, thereby ensuring that CN promotes it. However, radiotherapy may overcome immune resistance during oligoprogression.

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          Most cited references58

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          Macrophages as regulators of tumour immunity and immunotherapy

          Macrophages are critical mediators of tissue homeostasis, with tumors distorting this proclivity to stimulate proliferation, angiogenesis, and metastasis. This had led to an interest in targeting macrophages in cancer, and preclinical studies have demonstrated efficacy across therapeutic modalities and tumor types. Much of the observed efficacy can be traced to the suppressive capacity of macrophages, driven by microenvironmental cues such as hypoxia and fibrosis. As a result, tumor macrophages display an ability to suppress T cell recruitment and function as well as regulate other aspects of tumor immunity. With the increasing impact of cancer immunotherapy, macrophage targeting is now being evaluated in this context. Here we will discuss the results of clinical trials and the future of combinatorial immunotherapy.
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            Coordinated regulation of myeloid cells by tumours.

            Myeloid cells are the most abundant nucleated haematopoietic cells in the human body and are a collection of distinct cell populations with many diverse functions. The three groups of terminally differentiated myeloid cells - macrophages, dendritic cells and granulocytes - are essential for the normal function of both the innate and adaptive immune systems. Mounting evidence indicates that the tumour microenvironment alters myeloid cells and can convert them into potent immunosuppressive cells. Here, we consider myeloid cells as an intricately connected, complex, single system and we focus on how tumours manipulate the myeloid system to evade the host immune response.
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              Irradiation and anti-PD-L1 treatment synergistically promote antitumor immunity in mice.

              High-dose ionizing irradiation (IR) results in direct tumor cell death and augments tumor-specific immunity, which enhances tumor control both locally and distantly. Unfortunately, local relapses often occur following IR treatment, indicating that IR-induced responses are inadequate to maintain antitumor immunity. Therapeutic blockade of the T cell negative regulator programmed death-ligand 1 (PD-L1, also called B7-H1) can enhance T cell effector function when PD-L1 is expressed in chronically inflamed tissues and tumors. Here, we demonstrate that PD-L1 was upregulated in the tumor microenvironment after IR. Administration of anti-PD-L1 enhanced the efficacy of IR through a cytotoxic T cell-dependent mechanism. Concomitant with IR-mediated tumor regression, we observed that IR and anti-PD-L1 synergistically reduced the local accumulation of tumor-infiltrating myeloid-derived suppressor cells (MDSCs), which suppress T cells and alter the tumor immune microenvironment. Furthermore, activation of cytotoxic T cells with combination therapy mediated the reduction of MDSCs in tumors through the cytotoxic actions of TNF. Our data provide evidence for a close interaction between IR, T cells, and the PD-L1/PD-1 axis and establish a basis for the rational design of combination therapy with immune modulators and radiotherapy.
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                Author and article information

                Contributors
                Journal
                Front Immunol
                Front Immunol
                Front. Immunol.
                Frontiers in Immunology
                Frontiers Media S.A.
                1664-3224
                15 June 2021
                2021
                : 12
                : 646085
                Affiliations
                [1] 1 Cheeloo College of Medicine, Shandong University , Jinan, China
                [2] 2 Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences , Jinan, China
                [3] 3 Health Research, Faculty of Health and Medicine, Lancaster University , City of Lancaster, United Kingdom
                Author notes

                Edited by: Ilaria Marigo, Veneto Institute of Oncology (IRCCS), Italy

                Reviewed by: Weidong Han, Sir Run Run Shaw Hospital, China; Georgi Guruli, Virginia Commonwealth University, United States; Wan Xiangbo, The Sixth Affiliated Hospital of Sun Yat-sen University, China

                *Correspondence: Xue Meng, mengxuesdzl@ 123456163.com ; Jinbo Yue, jbyue@ 123456sdfmu.edu.cn

                This article was submitted to Cancer Immunity and Immunotherapy, a section of the journal Frontiers in Immunology

                Article
                10.3389/fimmu.2021.646085
                8239433
                34211459
                dc3ad9d4-be71-4a2d-a67f-ce75bdfd846a
                Copyright © 2021 Wu, Liu, Seery, Meng and Yue

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 25 December 2020
                : 28 May 2021
                Page count
                Figures: 4, Tables: 0, Equations: 0, References: 58, Pages: 9, Words: 3539
                Funding
                Funded by: Foundation for Innovative Research Groups of the National Natural Science Foundation of China 10.13039/501100012659
                Categories
                Immunology
                Case Report

                Immunology
                clear cell renal cell carcinoma,camrelizumab,abscopal effect,pseudoprogression,mlr
                Immunology
                clear cell renal cell carcinoma, camrelizumab, abscopal effect, pseudoprogression, mlr

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