Biomarkers for Predicting Efficacies of Anti-PD1 Antibodies

Kambayashi, Yahiko; Fujimura, Taku; Hidaka, Takanori; Aiba, Setsuya

doi:10.3389/fmed.2019.00174

Cited by 50 publications

(59 citation statements)

References 53 publications

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“…Since the response rates to ICI treatment are still restricted [26][27][28][29]83], the identification of response-biomarkers before or shortly after the therapy initiation is one of the biggest challenges in the immuno-oncology. Current approaches to predict response to ICI in melanoma are based on the radiology, tumor biopsy and liquid biopsy [84,85].…”

Section: Predicting the Response To The Ici Therapymentioning

confidence: 99%

“…Besides PD-L1, soluble CD163 and macrophage-related chemokines (e.g., C-X-C motif chemokine ligand (CXCL) 5, 10) were reported to predict efficacy of ICI [85]. Decreased serum levels of IL-8 at 2 to 4 weeks after the start of ICI treatment were associated with the response in patients even with the initial pseudoprogression [99].…”

Section: Predicting the Response To The Ici Therapymentioning

confidence: 99%

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Modern Aspects of Immunotherapy with Checkpoint Inhibitors in Melanoma

Petrova

Arkhypov

Weber

et al. 2020

IJMS

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Although melanoma is one of the most immunogenic tumors, it has an ability to evade anti-tumor immune responses by exploiting tolerance mechanisms, including negative immune checkpoint molecules. The most extensively studied checkpoints represent cytotoxic T lymphocyte-associated protein-4 (CTLA-4) and programmed cell death protein 1 (PD-1). Immune checkpoint inhibitors (ICI), which were broadly applied for melanoma treatment in the past decade, can unleash anti-tumor immune responses and result in melanoma regression. Patients responding to the ICI treatment showed long-lasting remission or disease control status. However, a large group of patients failed to respond to this therapy, indicating the development of resistance mechanisms. Among them are intrinsic tumor properties, the dysfunction of effector cells, and the generation of immunosuppressive tumor microenvironment (TME). This review discusses achievements of ICI treatment in melanoma, reasons for its failure, and promising approaches for overcoming the resistance. These methods include combinations of different ICI with each other, strategies for neutralizing the immunosuppressive TME and combining ICI with other anti-cancer therapies such as radiation, oncolytic viral, or targeted therapy. New therapeutic approaches targeting other immune checkpoint molecules are also discussed.

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Section: Predicting the Response To The Ici Therapymentioning

confidence: 99%

Section: Predicting the Response To The Ici Therapymentioning

confidence: 99%

Modern Aspects of Immunotherapy with Checkpoint Inhibitors in Melanoma

Petrova

Arkhypov

Weber

et al. 2020

IJMS

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“…Die Ansprechraten auf die Behandlung mit ICI sind weiterhin begrenzt [26-29, 83] und eine der größten Herausforderungen in der Immunonkologie besteht deshalb darin, Response-Biomarker vor oder kurz nach Therapiebeginn zu identifizieren. Aktuelle Ansätze zur Vorhersage des Ansprechens von Melanom-Patienten auf die ICI-Therapie basieren auf radiologischen Untersuchungen, Tumorbiopsie und Liquid Biopsy [84, 85].…”

Section: Vorhersage Des Ansprechens Auf Die Ici-therapieunclassified

Moderne Aspekte der Immuntherapie mit Checkpoint-Inhibitoren bei Melanom

et al. 2020

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Das Melanom gehört zu den am stärksten immunogenen Tumoren. Dennoch ist es in der Lage, sich einer antitumoralen Immunantwort zu entziehen, indem es Toleranzmechanismen, einschließlich negativer Immuncheckpoint-Moleküle, nutzt. Die am umfassendsten untersuchten Immuncheckpoints sind CTLA-4 (cytotoxic T lymphocyte-associated protein-4) und PD-1 (programmed cell death protein 1). Immuncheckpoint-Inhibitoren (ICI), die in den vergangenen 10 Jahren häufig zur Behandlung von Melanomen eingesetzt wurden, können antitumorale Immunreaktionen auslösen und eine Rückbildung des Melanoms bewirken. Patienten, die auf die ICI-Behandlung ansprachen, erreichten eine langanhaltende Remission oder einen Zustand der Krankheitskontrolle. Eine große Gruppe von Patienten sprach dagegen nicht auf diese Therapie an, was darauf hindeutet, dass es zu einer Entwick

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“…To avoid misprediction by IHC staining, Conroy et al assessed the expression of PD-L1, using next-generation RNA sequencing, but the sensitivity of their system resembles that of IHC assay systems and is, in addition, more expensive [58]. Additional assays or completely different assay systems will be needed in the future to diagnose PD-L1 expression of patient cancer tissues, for the prediction of clinical outcomes for the ICI treatment of melanoma [60].…”

Section: Patients With Cancermentioning

confidence: 99%

Humanized Mice as an Effective Evaluation System for Peptide Vaccines and Immune Checkpoint Inhibitors

Kametani

Ohno

Ohshima

et al. 2019

IJMS

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Peptide vaccination was developed for the prevention and therapy of acute and chronic infectious diseases and cancer. However, vaccine development is challenging, because the patient immune system requires the appropriate human leukocyte antigen (HLA) recognition with the peptide. Moreover, antigens sometimes induce a low response, even if the peptide is presented by antigen-presenting cells and T cells recognize it. This is because the patient immunity is dampened or restricted by environmental factors. Even if the immune system responds appropriately, newly-developed immune checkpoint inhibitors (ICIs), which are used to increase the immune response against cancer, make the immune environment more complex. The ICIs may activate T cells, although the ratio of responsive patients is not high. However, the vaccine may induce some immune adverse effects in the presence of ICIs. Therefore, a system is needed to predict such risks. Humanized mouse systems possessing human immune cells have been developed to examine human immunity in vivo. One of the systems which uses transplanted human peripheral blood mononuclear cells (PBMCs) may become a new diagnosis strategy. Various humanized mouse systems are being developed and will become good tools for the prediction of antibody response and immune adverse effects.

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Biomarkers for Predicting Efficacies of Anti-PD1 Antibodies

Cited by 50 publications

References 53 publications

Modern Aspects of Immunotherapy with Checkpoint Inhibitors in Melanoma

Modern Aspects of Immunotherapy with Checkpoint Inhibitors in Melanoma

Moderne Aspekte der Immuntherapie mit Checkpoint-Inhibitoren bei Melanom

Humanized Mice as an Effective Evaluation System for Peptide Vaccines and Immune Checkpoint Inhibitors

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