Immunotherapies: The Blockade of Inhibitory Signals

Wu, Yanling; Liang, Jing; Zhang, Wen; Tanaka, Yoshimasa; Sugiyama, Hiroshi

doi:10.7150/ijbs.5273

Cited by 28 publications

(20 citation statements)

References 98 publications

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“…37,38). Similar results may be obtained when radiotherapy is combined with blockade of other coinhibitory molecules, such as Tim-3, PD-1, or BTLA (39)(40)(41). A recent study has shown that anti-PD-1 antibody produced objective responses, 1 in 4 to 1 in 5 patients with advanced nonsmall cell lung cancer, melanoma, or renal-cell cancer (42).…”

Section: Discussionmentioning

confidence: 59%

Radiotherapy of Human Sarcoma Promotes an Intratumoral Immune Effector Signature

Sharma

Bode

Studer

et al. 2013

Clinical Cancer Research

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Purpose: The tumor immune microenvironment plays a crucial role in the development and progression of cancer. Sarcomas are a group of heterogeneous soft tissue malignancies that are often treated with radiotherapy as a part of the treatment concept. There is increasing evidence that radiotherapy leads to alterations in the tumor microenvironment, particularly with respect to the immune infiltrate. This study has been carried out to develop a better understanding of such changes following radiotherapy.Experimental Design: We retrospectively analyzed the expression of 35 immune response-related genes by quantitative reverse transcription PCR analysis and immunohistochemistry on paired formalin-fixed paraffin-embedded tumor samples from 38 sarcoma patients before and after radiotherapy.Results: We observed that radiotherapy results in a significant upregulation of several immune effectors and cancer-testis antigens and a concomitant downregulation of immune suppressors, indicating that radiotherapy may support the immune defense in sarcomas.Conclusions: These novel findings may have implications for the design of therapeutic regimens which exploite the immune system in sarcoma patients by combining standard radiotherapy with immunotherapeutic strategies.

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Section: Discussionmentioning

confidence: 59%

Radiotherapy of Human Sarcoma Promotes an Intratumoral Immune Effector Signature

Sharma

Bode

Studer

et al. 2013

Clinical Cancer Research

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“…Several monoclonal antibodies (mAbs) that block these proteins were developed to Ivyspring International Publisher down-regulate the inhibitory immune response, and promote the cellular cytotoxicity of T cells that eliminate tumor cells [6]. Among the immune checkpoint-blocking drugs, the inhibitors targeting PD-1 or CTLA4 were successfully used for treating patients with metastatic melanoma, with improved responses and prolonged survival [7]. This success led to the development of such agents for treating a wide range of malignancies, including renal cell carcinoma (RCC) [8], NSCLC [9][10][11], and acute myeloid leukemia (AML) [12], which further enhanced the response rate compared to conventional treatments, and prolonged the survival time of patients.…”

Section: B7 Familymentioning

confidence: 99%

B7-H3, a checkpoint molecule, as a target for cancer immunotherapy

2020

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B7-H3 (also known as CD276) is a newly found molecule of B7 family, which may be a promising target for cancer treatment. B7-H3 protein was demonstrated to be expressed in several kinds of tumor tissues including non-small-cell lung cancer (NSCLC) and prostate cancer. Its expression is highly associated with undesirable treatment outcomes and survival time, due to function of the immune checkpoint molecule. It was classified as either a co-stimulatory molecule for T cell activation or the nonimmunological role of regulating signaling pathways. Although there is still no agreed conclusion on the function of B7-H3, it may be a valuable target for cancer therapy. This review aims to provide a comprehensive, up-to-date summary of the advances in B7-H3 targeting approaches in cancer therapy. Although several challenges remain, B7-H3 offers a new therapeutic target with increased efficacy and less toxicity in future cancer treatment.

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“…PD-1 występuje na limfocytach cytotoksycznych, ligand dla PD-1-PD-L1 występuje w nadmiarze na komórkach guza. Interakcja PD-1 z PD-L1 ma silną funkcję immunosupresyjną poprzez hamowanie wydzielania cytokin oraz supresję aktywności cytolitycznej limfocytów [86,87]. W badaniach klinicznych wykazano skuteczność humanizowanych przeciwciał monoklonalnych, który funkcja polega na hamowaniu połączenia receptora PD-1 z ligandem.…”

Section: Implikacje Terapeutyczne -Metody Immunoterapii W Raku Płucaunclassified

Zaburzenia odpowiedzi immunologicznej w raku płuca—Nowy cel terapii

Domagała‐Kulawik

Osińska²

2014

Advances in Respiratory Medicine

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Lung cancer is the main cause of cancer death worldwide. An advanced stage of the disease at the time of diagnosis, observed in the majority of cases, does not allow for introduction of radical treatment or makes the treatment ineffective. Lung cancer as a solid tumour with a very low antigenicity escapes immune surveillance, and cytotoxic cells attack. Cytotoxic lymphocytes play a key role in anticancer defence, but the population of these cells individually differs. Many suppressor and regulatory mechanisms inhibit the recognition of tumour antigens by dendritic and cytotoxic cell activation. The population of regulatory T cells (T regs) plays a crucial role in this inhibition of immune response. Their function depends on the expression of transcription factor Foxp3 and the presence of CTLA-4 molecules. The increased proportion of T regs and high expression of Foxp3 and CTLA-4 on lung cancer cells and tumour infiltrating lymphocytes were observed. Other components of immune response inhibition and tumour promotion are: Th17 cell population, M2 macrophage polarisation, the presence of myeloid derived suppressor cells (MDSCs) and a significantly elevated concentration of cytokines: TGF-b and IL-10 in the tumour microenvironment. The recognition of these mechanisms may have important therapeutic implications. Several types of agents which are capable of modulating the immune response have recently been used in many clinical trials conducted in lung cancer patients, some of them showing efficacy. Lung cancer immunotherapy has two main directions: the first goal is to improve the cytotoxic effect (for example by inhibition of CTLA-4, stimulation of dendritic cell function, inhibition of lymphocyte apoptosis), and the second way is the production of anti-cancer vaccines using known cancer antigens: MAGE A3, MUC1, EGF and TGF-b. Immunotherapy in lung cancer treatment has a character of personalised therapy - there is a need to specify the patient's immune status prior to treatment. The analysis of immune cells and mediators in the peripheral blood allows this, but the more valuable method seems to be bronchoalveolar lavage (BAL) examination with careful assessment of the tumour microenvironment.

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Immunotherapies: The Blockade of Inhibitory Signals

Cited by 28 publications

References 98 publications

Radiotherapy of Human Sarcoma Promotes an Intratumoral Immune Effector Signature

Radiotherapy of Human Sarcoma Promotes an Intratumoral Immune Effector Signature

B7-H3, a checkpoint molecule, as a target for cancer immunotherapy

Zaburzenia odpowiedzi immunologicznej w raku płuca—Nowy cel terapii

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