Beyond T Cells: Understanding the Role of PD-1/PD-L1 in Tumor-Associated Macrophages

Lu, Di; Ni, Zhen; Liu, Xiguang; Feng, Siyang; Dong, Xiaoying; Shi, Xiaoshun; Zhai, Jianxue; Mai, Shijie; Jiang, Jianjun; Wang, Zhizhi; Wu, Hua; Cai, Kaican

doi:10.1155/2019/1919082

Cited by 109 publications

(97 citation statements)

References 48 publications

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“…As PD‐L1 does not act alone and future studies should consider the expression of its receptor, PD‐1, past studies have found that the measurement of both PD‐L1 and PD‐1 was a better predictor of survival than either factor alone (Maruse et al., 2018). PD‐L1 is also known to be expressed on tumour‐associated macrophages (TAMs), where it may encourage a M2‐phenotype, which is thought to be immunosuppressive (Lu et al., 2019). Shifting TAMs from a M2 to a M1 phenotype (proinflammatory) may be a therapeutic option in cancers, and the PD‐1/PD‐L1 pathway may be a potential target for this (Lu et al., 2019).…”

Section: Discussionmentioning

confidence: 99%

“…PD‐L1 is also known to be expressed on tumour‐associated macrophages (TAMs), where it may encourage a M2‐phenotype, which is thought to be immunosuppressive (Lu et al., 2019). Shifting TAMs from a M2 to a M1 phenotype (proinflammatory) may be a therapeutic option in cancers, and the PD‐1/PD‐L1 pathway may be a potential target for this (Lu et al., 2019).…”

Section: Discussionmentioning

confidence: 99%

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Clinicopathological and prognostic significance of PD‐L1 in oral cancer: A preliminary retrospective immunohistochemistry study

et al. 2020

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Objective To evaluate the relation between PD‐L1 expression in oral cavity squamous cell carcinomas and clinicopathological features as well as survival outcomes. Methods A retrospective immunohistochemical study was carried out on 55 archived tumours from 55 patients. Tumours were stained for PD‐L1 and scored by the proportion of tumour cells with positive membranous staining. PD‐L1 scores were compared to the patient's clinicopathological characteristics for any significant associations. Kaplan–Meier curves were constructed for PD‐L1 positive and negative tumours to investigate any advantage to survival. Results Positive PD‐L1 staining was found in 58% of tumours and was significantly more likely in non‐smokers, non‐drinkers and in tongue squamous cell carcinomas. Increased PD‐L1 was also associated with increased lymphocyte infiltration as well as PD‐L1 staining in lymphocytes and the epithelium adjacent to tumour invasion. No survival benefit was seen from PD‐L1 expression in tumour cells. Conclusions PD‐L1 expression is more common in non‐smokers and non‐drinkers, and its presence in the adjacent non‐tumour epithelium suggests it may be involved in early oncogenesis.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Clinicopathological and prognostic significance of PD‐L1 in oral cancer: A preliminary retrospective immunohistochemistry study

et al. 2020

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“…Tumor associated macrophages (TAM) are the most abundant immune cells and are known to differentially regulate tumor progression [ 22 , 23 ]. TAM also express both PD-1 and PD-L1 on their cell surface [ 24 ]. The tumor supportive “M2” macrophages express higher levels of PD-1 as compared with tumor suppressive “M1” macrophages.…”

Section: Introductionmentioning

confidence: 99%

The Confounders of Cancer Immunotherapy: Roles of Lifestyle, Metabolic Disorders and Sociological Factors

Deshpande

Sharma

Watabe

2020

Cancers

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Checkpoint blockade immunotherapy (CPI) is an effective treatment option for many types of cancers. Irrespective of its wide clinical implications, the overall efficacy remains unpredictable and even poor in certain pathologies such as breast cancer. Thus, it is imperative to understand the role of factors affecting its responsiveness. In this review, we provide an overview on the involvement of sociological factors, lifestyles and metabolic disorders in modulating the CPI response in patients from multiple malignancies. Lifestyle habits including exercise, and diet promoted therapeutic responsiveness while alcohol consumption mitigated the CPI effect by decreasing mutational burden and hampering antigen presentation by dendritic cells. Metabolic disorder such as obesity was recognized to enhance the PD-1 expression while diabetes and hypertension were consequences of CPI therapy rather than causes. Among the sociologic factors, sex and race positively influenced the CPI effectiveness on account of increased effector T cell activity and increased PD-1 expression while ageing impaired CPI responsiveness by decreasing functional T cell and increased toxicity. The combined effect of these factors was observed for obesity and gender, in which obese males had the most significant effect of CPI. Therefore these variables should be carefully considered before treating patients with CPI for optimal treatment outcome.

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“…It has also been reported that signaling via CD40 promotes IL-9 receptor expression on the surface of mBCs, and IL-9 promotes differentiation mBCs into PCs through the IL-9 receptor [1,82]. B7H-2 binds ICOS found on CD4/CD8 T cells, and enhances secretion of IFN-γ and IL-10, which sustain immune balance [84][85][86][87][88].…”

Section: B-2 Cellsmentioning

confidence: 97%

Characteristics of Immunoglobulin M Type Antibodies of Different Origins from the Immunologic and Clinical Viewpoints and Their Application in Controlling Antibody-Mediated Allograft Rejection

Matsuda

Hiramitsu

et al. 2020

Pathogens

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Antibody-mediated allograft rejection (AMR) hinders patient prognosis after organ transplantation. Current studies concerning AMR have mainly focused on the diagnostic value of immunoglobulin G (IgG)-type donor-specific antihuman leukocyte antigen antibodies (DSAs), primarily because of their antigen specificity, whereas the clinical significance of immunoglobulin M (IgM)-type DSAs has not been thoroughly investigated in the context of organ transplantation because of their nonspecificity against antigens. Although consensus regarding the clinical significance and role of IgM antibodies is not clear, as discussed in this review, recent findings strongly suggest that they also have a huge potential in novel diagnostic as well as therapeutic application for the prevention of AMR. Most serum IgM antibodies are known to comprise natural antibodies with low affinity toward antigens, and this is derived from B-1 cells (innate B cells). However, some of the serum IgM-type antibodies reportedly also produced by B-2 cells (conventional B cells). The latter are known to have a high affinity for donor-specific antigens. In this review, we initially discuss how IgM-type antibodies of different origins participate in the pathology of various diseases, directly or through cell surface receptors, complement activation, or cytokine production. Then, we discuss the clinical applicability of B-1 and B-2 cell-derived IgM-type antibodies for controlling AMR with reference to the involvement of IgM antibodies in various pathological conditions.

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Beyond T Cells: Understanding the Role of PD-1/PD-L1 in Tumor-Associated Macrophages

Cited by 109 publications

References 48 publications

Clinicopathological and prognostic significance of PD‐L1 in oral cancer: A preliminary retrospective immunohistochemistry study

Clinicopathological and prognostic significance of PD‐L1 in oral cancer: A preliminary retrospective immunohistochemistry study

The Confounders of Cancer Immunotherapy: Roles of Lifestyle, Metabolic Disorders and Sociological Factors

Characteristics of Immunoglobulin M Type Antibodies of Different Origins from the Immunologic and Clinical Viewpoints and Their Application in Controlling Antibody-Mediated Allograft Rejection

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