PD1/PD-L1 immune checkpoint as a potential target for preventing brain tumor progression

Filippone, Alessia; Lanza, Marika; Mannino, Deborah; Raciti, G.; Colarossi, Cristina; Sciacca, Dorotea; Cuzzocrea, Salvatore; Paterniti, Irene

doi:10.1007/s00262-021-03130-z

Cited by 37 publications

(21 citation statements)

References 45 publications

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“…7 In cancer, high PD-L1 expression allows the tumor to "hide" from the immune system, and thus PD-1/PD-L1 antibodies have been used in cancer immunotherapy. 15 In addition, Bregs express FasL belonging to the tumor necrosis factor protein family, which binds to Fas on both CD4 and CD8 T cells to induce apoptosis. [16][17][18] 3 | ROLE OF BREG IN CANCER…”

Section: Physiology Of Bregsmentioning

confidence: 99%

The dichotomy of regulatory B cells in cancer versus allergic disease

Dang,

Yu,

Galant‐Swafford

et al. 2023

Molecular Carcinogenesis

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Regulatory B cells (Bregs) are an immunosuppressive cell phenotype that affects the immune system by limiting the inflammatory cascade. Dysregulation of Bregs can interestingly play a dichotomous role in the pathophysiology of many diseases and is especially highlighted when examining cancer pathology compared to allergic disease. This study reviews the existing literature on Bregs and compares their role in allergic disease in contrast to cancer development. Upregulation of Bregs in cancer states has been associated with poor prognostic outcomes across various cancer types, and Breg proliferation was associated with chronic interferon signaling, activation of the BCR–BTK (B cell receptor‐Bruton's tyrosine kinase) pathway, and release of C–X–C motif ligand 13. In contrast, Breg dysfunction has been identified as a key mechanism in many allergic diseases, such as allergic asthma, allergic rhinitis, atopic dermatitis, and contact dermatitis. Development of Breg‐targeted immunotherapies is currently at the preclinical level, but strategies differentially focus on Breg depletion in cancer versus Breg stimulation in allergy. Our review highlights the divergent functions that Bregs play in cancer compared to allergy. We conclude that natural homeostasis hinges on a fine balance between the dichotomous role of Bregs—over or underactivation can result in a pathological state.

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Section: Physiology Of Bregsmentioning

confidence: 99%

The dichotomy of regulatory B cells in cancer versus allergic disease

Dang,

Yu,

Galant‐Swafford

et al. 2023

Molecular Carcinogenesis

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“…In fact, ICs pathways, more importantly, PD-1/PD-L1 and CD28/CTLA-4, are co-opted by tumors, altering expression of proteins to ease cancer cells' evasion from immune surveillance as a result of the inhibiting T cell responses [ 14 ]. The ICs pathways mainly deter various key signaling axes in T cells, such as phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) and extracellular signal-regulated kinase 1/2 (ERK)/mitogen-activated protein kinase (MAPK), resulting in T cell exhaustion [ 42 , 43 ]. Since the inhibitory activities of ICs are critically adjusted by their surface expression and signal transduction, targeting these axes offer efficient outcome in cancer patients [ 44 ].…”

Section: Immunotherapy For Rccmentioning

confidence: 99%

Clinical potential of PD-1/PD-L1 blockade therapy for renal cell carcinoma (RCC): a rapidly evolving strategy

et al. 2022

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Programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) blockade therapy has become a game-changing therapeutic approach revolutionizing the treatment setting of human malignancies, such as renal cell carcinoma (RCC). Despite the remarkable clinical activity of anti-PD-1 or anti-PD-L1 monoclonal antibodies, only a small portion of patients exhibit a positive response to PD-1/PD-L1 blockade therapy, and the primary or acquired resistance might ultimately favor cancer development in patients with clinical responses. In light of this, recent reports have signified that the addition of other therapeutic modalities to PD-1/PD-L1 blockade therapy might improve clinical responses in advanced RCC patients. Until, combination therapy with PD-1/PD-L1 blockade therapy plus cytotoxic T lymphocyte antigen 4 (CTLA-4) inhibitor (ipilimumab) or various vascular endothelial growth factor receptors (VEGFRs) inhibitors axitinib, such as axitinib and cabozantinib, has been approved by the United States Food and Drug Administration (FDA) as first-line treatment for metastatic RCC. In the present review, we have focused on the therapeutic benefits of the PD-1/PD-L1 blockade therapy as a single agent or in combination with other conventional or innovative targeted therapies in RCC patients. We also offer a glimpse into the well-determined prognostic factor associated with the clinical response of RCC patients to PD-1/PD-L1 blockade therapy.

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“…Based on these considerations, MDSC and T-reg cells are central immunosuppressive cells involved in the progression of brain tumors. Furthermore, PD-L1 expression in glioma cells has also shown great variance in several studies that attribute a therapeutic and prognostic biomarker role to PD-L1 in glioma [ 77 ]. PD-L1 expressed by glioma, in addition to increasing the number of T-reg cells, inhibits the functions of T lymphocytes and induces apoptosis of tumor-specific CD4+ and CD8+ T lymphocytes by decreasing the production of cytokines such as Inter-leukin-2 (IL-2) and interleukin-10 (IL-10) [ 78 , 79 ].…”

Section: Impact Of Kinase Inhibitors On Immune Systemmentioning

confidence: 99%

Protein Kinase Inhibitors as a New Target for Immune System Modulation and Brain Cancer Management

Filippone

Mannino

Casili

et al. 2022

IJMS

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High-grade brain tumors are malignant tumors with poor survival and remain the most difficult tumors to treat. An important contributing factor to the development and progression of brain tumors is their ability to evade the immune system. Several immunotherapeutic strategies including vaccines and checkpoint inhibitors have been studied to improve the effectiveness of the immune system in destroying cancer cells. Recent studies have shown that kinase inhibitors, capable of inhibiting signal transduction cascades that affect cell proliferation, migration, and angiogenesis, have additional immunological effects. In this review, we explain the beneficial therapeutic effects of novel small-molecule kinase inhibitors and explore how, through different mechanisms, they increase the protective antitumor immune response in high-grade brain tumors.

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PD1/PD-L1 immune checkpoint as a potential target for preventing brain tumor progression

Cited by 37 publications

References 45 publications

The dichotomy of regulatory B cells in cancer versus allergic disease

The dichotomy of regulatory B cells in cancer versus allergic disease

Clinical potential of PD-1/PD-L1 blockade therapy for renal cell carcinoma (RCC): a rapidly evolving strategy

Protein Kinase Inhibitors as a New Target for Immune System Modulation and Brain Cancer Management

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