Future prospects of immune checkpoint blockade in cancer: from response prediction to overcoming resistance

Park, Young-Jun; Kuen, Da-Sol; Chung, Yeonseok

doi:10.1038/s12276-018-0130-1

Cited by 168 publications

(131 citation statements)

References 127 publications

(140 reference statements)

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“…The early laboratory development of immune checkpoint inhibitors (ICIs) has been reviewed in detail by others . In brief, James Allison and his colleagues were the first to outline the critical function of cytotoxic T lymphocyte‐associated protein 4 (CTLA‐4) as a negative regulator of T‐cell activation .…”

Section: Development and Early Establishment Of Immune Checkpoint Inhmentioning

confidence: 99%

Immune checkpoint inhibitors: The linchpins of modern immunotherapy

Wilky

2019

Immunological Reviews

167

113

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Immune checkpoint inhibitors (ICIs) have revolutionized our approach to cancer treatment in the past decade. While monoclonal antibodies to CTLA‐4 and PD‐1/PD‐L1 have produced remarkable and durable responses in a subset of patients, the majority of patients will still develop primary or adaptive resistance. With complex mechanisms of resistance limiting the efficacy of checkpoint inhibitor monotherapy, it is critical to develop combination approaches to allow more patients to benefit from immunotherapy. In this review, I approach the current landscape of ICI research from the perspective of sarcomas, a rare group of bone and soft tissue cancers that have had limited benefit from checkpoint inhibitor monotherapy, and little investigation of biomarkers to predict responses. By surveying the various mechanisms of resistance and treatment modalities being explored in other solid tumors, I outline how ICIs will undoubtedly serve as the critical foundation for future directions in modern immunotherapy.

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Section: Development and Early Establishment Of Immune Checkpoint Inhmentioning

confidence: 99%

Immune checkpoint inhibitors: The linchpins of modern immunotherapy

Wilky

2019

Immunological Reviews

167

113

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“…The response of PD1/PD‐L1 negative tumours to checkpoint inhibitors was unexpected. Dynamic expression of PD‐L1 and multifactorial determination of immunotherapy responses are the potential explanations . Some of the known resistance mechanisms are summarised in the biomarker section below and further mechanistic investigations are required.…”

Section: Mechanisms Of the Response To Anti‐pd1/pd‐l1 Immunotherapymentioning

confidence: 99%

“…The response of immunotherapies, even targeting specific immune response molecules such as in the case of anti‐PD‐1/PD‐L1 ICB, is determined by multiple factors, including cancer cell immunogenicity, TME and the strength of local/systematic immune activity . Therefore, we review the relevant literature of immunotherapy response predictors in consideration of these aspects.…”

Section: Biomarkers To Predict the Response Of Immune Therapiesmentioning

confidence: 99%

“…Predicting which patient will benefit from the expensive ICB immunotherapy is critical. Although the mechanism of anti‐PD‐1/PD‐L1 immunotherapy is simple, patient response is determined by multiple factors . Extensive research has been carried out with dozens of review articles on anti‐PD‐1/PD‐L1 immunotherapy biomarkers in the last 2 years.…”

Section: Biomarkers To Predict the Response Of Immune Therapiesmentioning

confidence: 99%

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Bladder cancer, a unique model to understand cancer immunity and develop immunotherapy approaches

Song

Powles

Shi

et al. 2019

The Journal of Pathology

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With the mechanistic understanding of immune checkpoints and success in checkpoint blockade using antibodies for the treatment of certain cancers, immunotherapy has become one of the hottest areas in cancer research, with promise of long‐lasting therapeutic effect. Currently, however, only a proportion of cancers have a good response to checkpoint inhibition immunotherapy. Better understanding of the cancer response and resistance mechanisms is essential to fully explore the potential of immunotherapy to cure the majority of cancers. Bladder cancer, one of the most common and aggressive malignant diseases, has been successfully treated both at early and advanced stages by different immunotherapeutic approaches, bacillus Calmette–Guérin (BCG) intravesical instillation and anti‐PD‐1/PD‐L1 immune checkpoint blockade, respectively. Therefore, it provides a good model to investigate cancer immune response mechanisms and to improve the efficiency of immunotherapy. Here, we review bladder cancer immunotherapy with equal weight on BCG and anti‐PD‐1/PD‐L1 therapies and demonstrate why and how bladder cancer can be used as a model to study the predictors and mechanisms of cancer immune response and shine light on further development of immunotherapy approaches and response predictive biomarkers to improve immunotherapy of bladder cancer and other malignancies. We review the success of BCG and anti‐PD‐1/PD‐L1 treatment of bladder cancer, the underlying mechanisms and the therapeutic response predictors, including the limits to our knowledge. We then highlight briefly the adaptation of immunotherapy approaches and predictors developed in other cancers for bladder cancer therapy. Finally, we explore the potential of using bladder cancer as a model to investigate cancer immune response mechanisms and new therapeutic approaches, which may be translated into immunotherapy of other human cancers. © 2019 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

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“…Immune checkpoints are inhibitory pathways responsible for regulating the immune responses to avoid excessive immune activity and keep the central and peripheral tolerance. 107 Monoclonal antibodies designed to block such immune checkpoints are known as immune checkpoint blockers, reestablish the tumor-specific cellular immune responses against the cancerous cells. 108 There is growing evidence that monoclonal antibody therapy using anti-CTLA-4, programmed death-1, and CD137 (4-1BB) monoclonal antibodies can enhance antitumor immunity.…”

Section: Prospects In Adoptive Cell Transfermentioning

confidence: 99%

Cell transfer‐based immunotherapies in cancer: A review

et al. 2019

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In cell transfer therapy (CTT), immune cells such as innate immune‐derived natural killer cells and dendritic cells as well as acquired immune‐related T lymphocytes such as tumor‐infiltrating lymphocytes and cytokine‐activated or genetically modified peripheral blood T cells are used in the management of cancer. These therapies are increasingly becoming the most used treatment modality in cancer after tumor resection, chemotherapy, and radiotherapy. In adoptive cell transfer, the lymphocytes isolated from either a donor or the patient are modified ex vivo and reinfused to target malignant cells. Transferring in vitro‐manipulated immune cells produces a continuous antitumor immune response. In this review, we evaluate the recent advances in CTT for the management of various malignancies.

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Future prospects of immune checkpoint blockade in cancer: from response prediction to overcoming resistance

Cited by 168 publications

References 127 publications

Immune checkpoint inhibitors: The linchpins of modern immunotherapy

Immune checkpoint inhibitors: The linchpins of modern immunotherapy

Bladder cancer, a unique model to understand cancer immunity and develop immunotherapy approaches

Cell transfer‐based immunotherapies in cancer: A review

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