Immunotherapy for Ovarian Cancer: Adjuvant, Combination, and Neoadjuvant

Frontiers in Immunology, Journal Year: 2020, Volume and Issue: 11

Published: Oct. 6, 2020

Ovarian cancer is the most lethal gynecologic malignancy. Surgery and chemotherapy are primary treatments for ovarian cancer; however, patients often succumb to recurrence with chemotherapeutic resistance within several years after initial treatment. In past two decades, immunotherapy has rapidly developed revolutionize treatment of various types cancer. Despite fact that response rates among remain modest, immune checkpoint inhibitors (ICIs), chimeric antigen receptor (CAR)- TCR-engineered T cells developing. Therapeutic efficiency could be improved significantly if included as an adjuvant therapy, in combination chemotherapy, radiation anti-angiogenesis drugs, poly ADP ribose polymerase (PARPi). Newly technologies identify therapeutic targets, predict efficacy, screen potential provide neoadjuvant immunotherapy, utilize nanomedicine technology new opportunities have prolong patient survival. However, important issues may hinder efficacy such approaches, including hyperprogressive disease (HPD), immunotherapy-resistance, toxicity treatments, neurotoxicity, must taken into account addressed these therapies effective.

Language: Английский

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Roles of BTLA in Immunity and Immune Disorders

Frontiers in Immunology, Journal Year: 2021, Volume and Issue: 12

Published: March 29, 2021

B and T lymphocyte attenuator (BTLA) is one of the most important cosignaling molecules. It belongs to CD28 superfamily similar programmed cell death-1 (PD-1) cytotoxic associated antigen-4 (CTLA-4) in terms its structure function. BTLA can be detected lymphocytes induces immunosuppression by inhibiting activation proliferation. The ligand, herpesvirus entry mediator (HVEM), does not belong classic B7 family. Instead, it a member tumor necrosis factor receptor (TNFR) superfamily. association with HVEM directly bridges TNFR families mediates broad powerful immune effects. Recently, large number studies have found that participates numerous physiopathological processes, such as tumor, inflammatory diseases, autoimmune infectious transplantation rejection. Therefore, present work aimed review existing knowledge about immunity summarize diverse functions various disorders.

Language: Английский

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TGF-β, EMT, and resistance to anti-cancer treatment

Seminars in Cancer Biology, Journal Year: 2023, Volume and Issue: 97, P. 1 - 11

Published: Nov. 8, 2023

Transforming growth factor-β (TGF-β) signaling regulates cell-specific programs involved in embryonic development, wound-healing, and immune homeostasis. Yet, during tumor progression, these TGF-β-mediated are altered, leading to epithelial cell plasticity a reprogramming of cells into mesenchymal lineages through epithelial-to-mesenchymal transition (EMT), critical developmental program morphogenesis organogenesis. These changes, turn, lead enhanced carcinoma invasion, metastasis, differentiation, evasion, chemotherapy resistance. Here, we discuss EMT as one the associated with influence exerted by TGF-β on status function. We further explore composition other populations within microenvironment, consider relevant outcomes related cancer treatment

Language: Английский

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Beyond the anti-PD-1/PD-L1 era: promising role of the BTLA/HVEM axis as a future target for cancer immunotherapy

Molecular Cancer, Journal Year: 2023, Volume and Issue: 22(1)

Published: Aug. 30, 2023

Recent introduction of monoclonal antibodies targeting immune checkpoints to harness antitumor immunity has revolutionized the cancer treatment landscape. The therapeutic success checkpoint blockade (ICB)-based therapies mainly relies on PD-1/PD-L1 and CTLA-4 blockade. However, limited overall responses lack reliable predictive biomarkers patient´s response are major pitfalls limiting immunotherapy success. Hence, this reflects compelling need unveiling novel targets for that allow expand spectrum ICB-based strategies achieve optimal efficacy benefit patients. This review thoroughly dissects current molecular functional knowledge BTLA/HVEM axis future perspectives become a target immunotherapy. dysregulation is commonly found linked poor prognosis in solid hematological malignancies. Moreover, circulating BTLA been revealed as blood-based biomarker various cancers. On basis, emerges promising prompted rapid development clinical testing anti-BTLA blocking antibody Tifcemalimab/icatolimab first BTLA-targeted therapy ongoing phase I trials with encouraging results preliminary safety profile monotherapy combined other anti-PD-1/PD-L1 therapies. Nevertheless, it anticipated intricate signaling network constituted by BTLA/HVEM/CD160/LIGHT involved regulation, tumor microenvironment could limit Therefore, in-depth characterization different settings highly recommended adequate design implementation guarantee best outcomes

Language: Английский

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BTLA biology in cancer: from bench discoveries to clinical potentials

Biomarker Research, Journal Year: 2024, Volume and Issue: 12(1)

Published: Jan. 17, 2024

Abstract Immune checkpoints play a critical role in maintaining the delicate balance of immune activation order to prevent potential harm caused by excessive activation, autoimmunity, or tissue damage. B and T lymphocyte attenuator (BTLA) is one crucial checkpoint, regulating stimulatory inhibitory signals responses. Its interaction with herpes virus entry mediator (HVEM) plays an essential negatively responses, thereby preserving homeostasis. In cancer, abnormal cells evade surveillance exploiting like BTLA. Upregulated BTLA expression linked impaired anti-tumor immunity unfavorable disease outcomes. preclinical studies, BTLA-targeted therapies have shown improved treatment outcomes enhanced antitumor immunity. This review aims provide in-depth understanding BTLA’s biology, its various cancers, as prognostic factor. Additionally, it explores latest research on blockade cancer immunotherapy, offering hope for more effective treatments.

Language: Английский

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Adoptive cell therapy in combination with checkpoint inhibitors in ovarian cancer

Oncotarget, Journal Year: 2020, Volume and Issue: 11(22), P. 2092 - 2105

Published: June 2, 2020

Immune therapy is a promising field within oncology but has been unsuccessful in ovarian cancer (OC). Still, there rationale and evidence supporting immune OC. We investigated the potential for adoptive cell (ACT) from vitro expanded tumor-infiltrating lymphocytes (TILs) combination with checkpoint inhibitors (ICI) conducted immunological testing of ex vivo TILs (REP-TILs). Six patients late-stage metastatic high-grade serous OC were treated consisting ipilimumab followed by surgery to obtain infusion REP-TILs, low-dose IL-2 nivolumab. One patient achieved partial response 5 others experienced disease stabilization up 12 months. Analysis REP-TILs flow- mass-cytometry show primarily activated differentiated effector memory T cells. showed reactivity expression inhibitory receptors, such as LAG-3 PD-1. Furthermore, our data indicate that addition improves fold expansion during production, increase level CD8 tumor reactivity, favorably affect phenotype. ICI ACT feasible safe. With one long-lasting SD, we demonstrated

Language: Английский

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Soluble B7-CD28 Family Inhibitory Immune Checkpoint Proteins and Anti-Cancer Immunotherapy

Frontiers in Immunology, Journal Year: 2021, Volume and Issue: 12

Published: Aug. 31, 2021

Co-inhibitory B7-CD28 family member proteins negatively regulate T cell responses and are extensively involved in tumor immune evasion. Blockade of classical CTLA-4 (cytotoxic lymphocyte-associated antigen-4) PD-1 (programmed death protein-1) checkpoint pathways have become the cornerstone anti-cancer immunotherapy. New inhibitory such as B7-H3, B7-H4, BTLA (B lymphocyte attenuator) being discovered investigated for their potential In addition, soluble forms these molecules also exist sera healthy individuals elevated levels found chronic infections, autoimmune diseases, cancers. Soluble generated by proteolytic shedding or alternative splicing. Elevated circulating cancer been correlated with advance stage, metastatic status, prognosis which underscore broader involvement regulation. addition to biomarker, understanding mechanism production, biological activity, pathological interactions may pave way clinical use a therapeutic target. Here we review aspects elucidate on

Language: Английский

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Blockade of novel immune checkpoints and new therapeutic combinations to boost antitumor immunity

Journal of Experimental & Clinical Cancer Research, Journal Year: 2022, Volume and Issue: 41(1)

Published: Feb. 14, 2022

Abstract Immunotherapy has emerged as a promising strategy for boosting antitumoral immunity. Blockade of immune checkpoints (ICs), which regulate the activity cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells proven clinical benefits. Antibodies targeting CTLA-4, PD-1, PD-L1 are IC-blockade drugs approved treatment various solid hematological malignancies. However, large subset patients does not respond to current anti-IC immunotherapy. An integrative understanding tumor-immune infiltrate, IC expression function in cell populations is fundamental design effective therapies. The simultaneous blockade newly identified ICs, well previously described could improve antitumor response. We review potential novel combinatory strategies therapy, their effects on expressing targeted ICs. Preclinical evidence trials involving ICs reported. finally discuss rationale co-blockade with respect its downstream signaling order immunity prevent an increased risk immune-related adverse events (irAEs).

Language: Английский

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Immune checkpoint inhibition mediated with liposomal nanomedicine for cancer therapy

Military Medical Research, Journal Year: 2023, Volume and Issue: 10(1)

Published: April 28, 2023

Immune checkpoint blockade (ICB) therapy for cancer has achieved great success both in clinical results and on the market. At same time, drives more attention from scientists to improve it. However, only a small portion of patients are responsive this therapy, it comes with unique spectrum side effects termed immune-related adverse events (irAEs). The use nanotechnology could ICBs' delivery tumor, assist them penetrating deeper into tumor tissues alleviate their irAEs. Liposomal nanomedicine been investigated used decades, is well-recognized as most successful nano-drug system. combination ICB liposomal help efficacy therapy. In review, we highlighted recent studies using (including new emerging exosomes inspired nano-vesicles) associating

Language: Английский

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Recent Advancements in the Mechanisms Underlying Resistance to PD-1/PD-L1 Blockade Immunotherapy

Cancers, Journal Year: 2021, Volume and Issue: 13(4), P. 663 - 663

Published: Feb. 7, 2021

Release of immunoreactive negative regulatory factors such as immune checkpoint limits antitumor responses. PD-L1 a significant immunosuppressive factor has been involved in resistance to therapies chemotherapy and target therapy various cancers. Via interacting with PD-1, can regulate other or lead evasion cancer cells. Besides, blockade targeting PD-1/PD-L1 promising therapeutic efficacy the different tumors, but percentage patients cannot benefit from this due primary acquired during treatment. In review, we described utility expression levels for predicting poor prognosis some tumors present evidence role through pathway correlating signaling pathways. Afterwards, elaborate key mechanisms underlying immunotherapy. Furthermore, combination strategies resistant associated was also summarized.

Language: Английский

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