PD-L1/PD-1 Axis in Multiple Myeloma Microenvironment and a Possible Link with CD38-Mediated Immune-Suppression

Costa, Federica; Marchica, Valentina; Storti, Paola; Malavasi, Fabio; Giuliani, Nicola

doi:10.3390/cancers13020164

Cited by 18 publications

(15 citation statements)

References 101 publications

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“…PD-L1 can inhibit T cell proliferation and cytokine secretion, and negatively regulate lymphocyte activation 12 . PD-L1 can be expressed on the surface of tumor 13 . By binding to PD-1 on the surface of T cells, it induces apoptosis, incapacity and depletion of T cells, and then inhibits the activation, proliferation and anti-tumor function of tumor antigen-specific CD8+T cells to achieve tumor immune escape 14 .…”

Section: Discussionmentioning

confidence: 99%

PD-L1 correlated gene expression profiles and tumor infiltrating lymphocytes in pancreatic cancer

Li¹,

Yin²,

Chen³

et al. 2021

Int. J. Med. Sci.

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Objective: To study the expression and clinical value of PD-L1 gene in pancreatic cancer, and to predict the role of PD-L1 gene in the development of pancreatic cancer. Methods: The pancreatic cancer datasets were downloaded from the Cancer Genome Atlas (TCGA) and the Oncomine to obtain the PD-L1 gene expression profile and clinical information. Bioinformatics methods were used to analyze the correlation between the expression level of PD-L1 gene in pancreatic cancer and clinicopathological indicators, as well as its influence on prognosis. GSEA and WGCNA analysis was performed to predict the possible pathways of PD-L1 gene regulation in pancreatic cancer. TIMER and MCP-counter were used for PD-L1 with immune infiltration. The genes interact with PD-L1 were also investigated by STING and immunoco-precipitation combined with mass spectrometry analysis (IP-MS). Results: In TCGA database, the overall survival of patients with high expression of PD-L1 gene was significantly lower than that of patients with low expression of PD-L1 gene (χ 2 = 12.52, P < 0.001). The samples with high expression of PD-L1 gene showed enrichment of 8 pathways including toll-like receptor signaling pathway and NOD receptor signaling pathway (P < 0.01, FDR < 0.05). Immune infiltration analysis suggested that PD-L1 were associated with monocytic lineage (r = 0.5). The proteins interacting with PD-L1 are mainly concentrated in RNA binding, ribosome, spliceosome and other biological processes or pathways. Conclusion: PD-L1 gene may play an important role in the development of pancreatic cancer and is expected to be a prognostic indicator of pancreatic cancer.

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Section: Discussionmentioning

confidence: 99%

PD-L1 correlated gene expression profiles and tumor infiltrating lymphocytes in pancreatic cancer

Li¹,

Yin²,

Chen³

et al. 2021

Int. J. Med. Sci.

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“…The discovery of immune checkpoint pathways, their role in the evasion from immune surveillance, and the development of blocking antibodies represent one of the greatest achievements in cancer treatment, which was also recently rewarded by the Nobel Prize [136]. The majority of studies in MM have focused on the inhibitory PD-1/PD-L1 pathway (Figure 4), but many more pathways are crucial for the function of the immune system and may be therapeutically manipulated [20].…”

Section: Immune Checkpoints Inhibitorsmentioning

confidence: 99%

Harnessing the Immune System to Fight Multiple Myeloma

Krejcik

Barnkob

Nyvold

et al. 2021

Cancers

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Multiple myeloma (MM) is a heterogeneous plasma cell malignancy differing substantially in clinical behavior, prognosis, and response to treatment. With the advent of novel therapies, many patients achieve long-lasting remissions, but some experience aggressive and treatment refractory relapses. So far, MM is considered incurable. Myeloma pathogenesis can broadly be explained by two interacting mechanisms, intraclonal evolution of cancer cells and development of an immunosuppressive tumor microenvironment. Failures in isotype class switching and somatic hypermutations result in the neoplastic transformation typical of MM and other B cell malignancies. Interestingly, although genetic alterations occur and evolve over time, they are also present in premalignant stages, which never progress to MM, suggesting that genetic mutations are necessary but not sufficient for myeloma transformation. Changes in composition and function of the immune cells are associated with loss of effective immune surveillance, which might represent another mechanism driving malignant transformation. During the last decade, the traditional view on myeloma treatment has changed dramatically. It is increasingly evident that treatment strategies solely based on targeting intrinsic properties of myeloma cells are insufficient. Lately, approaches that redirect the cells of the otherwise suppressed immune system to take control over myeloma have emerged. Evidence of utility of this principle was initially established by the observation of the graft-versus-myeloma effect in allogeneic stem cell-transplanted patients. A variety of new strategies to harness both innate and antigen-specific immunity against MM have recently been developed and intensively tested in clinical trials. This review aims to give readers a basic understanding of how the immune system can be engaged to treat MM, to summarize the main immunotherapeutic modalities, their current role in clinical care, and future prospects.

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“…The ability of LLPCs and MM cells to unlock this complex metabolic program differentiates them from the SLPCs [ 53 ]. Anaplerosis of the TCA cycle with glutamine and the downstream production of oncometabolites such as hydroxyglutarate, as well as release of immunomodulating ones such as adenosine (ADO), have also been documented in MM [ 59 ]. Of course, as the disease progresses from the MGUS to MM, increased independence from the BM microenvironment and increased modulation of the niche is observed.…”

Section: Metabolism Of the Most Common B Cell Malignanciesmentioning

confidence: 99%

Metabolic Swifts Govern Normal and Malignant B Cell Lymphopoiesis

Poulaki

Giannouli

2021

IJMS

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B lymphocytes are an indispensable part of the human immune system. They are the effective mediators of adaptive immunity and memory. To accomplish specificity against an antigen, and to establish the related immunologic memory, B cells differentiate through a complicated and strenuous training program that is characterized by multiple drastic genomic modifications. In order to avoid malignant transformation, these events are tightly regulated by multiple checkpoints, the vast majority of them involving bioenergetic alterations. Despite this stringent control program, B cell malignancies are amongst the top ten most common worldwide. In an effort to better understand malignant pathobiology, in this review, we summarize the metabolic swifts that govern normal B cell lymphopoiesis. We also review the existent knowledge regarding malignant metabolism as a means to unravel new research goals and/or therapeutic targets.

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PD-L1/PD-1 Axis in Multiple Myeloma Microenvironment and a Possible Link with CD38-Mediated Immune-Suppression

Cited by 18 publications

References 101 publications

PD-L1 correlated gene expression profiles and tumor infiltrating lymphocytes in pancreatic cancer

PD-L1 correlated gene expression profiles and tumor infiltrating lymphocytes in pancreatic cancer

Harnessing the Immune System to Fight Multiple Myeloma

Metabolic Swifts Govern Normal and Malignant B Cell Lymphopoiesis

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