Combination Cancer Therapy with Immune Checkpoint Blockade: Mechanisms and Strategies

Patel, Shetal; Minn, Andy J.

doi:10.1016/j.immuni.2018.03.007

Cited by 471 publications

(357 citation statements)

References 174 publications

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“…It will be of interest to determine whether a similar reduced sensitivity to T cell attack by JAK1/2 mutations is selected for in epithelial cancers. In addition to the analysis of natural and therapy-induced variation in tumor cell sensitivity to T cell pressure, there is increasing interest in the use of small molecules and antibodies to enhance tumor cell sensitivity to T cell attack (Patel and Minn, 2018). Parallel tumor organoid – T cell cultures in the presence or absence of drugs of interest should form a straightforward system to identify suitable candidates for combination with immunotherapy.…”

Section: Discussionmentioning

confidence: 99%

Generation of Tumor-Reactive T Cells by Co-culture of Peripheral Blood Lymphocytes and Tumor Organoids

Dijkstra

Cattaneo

Weeber

et al. 2018

Cell

775

711

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Cancer immunotherapies have shown substantial clinical activity for a subset of patients with epithelial cancers. Still, technological platforms to study cancer T-cell interactions for individual patients and understand determinants of responsiveness are presently lacking. Here, we establish and validate a platform to induce and analyze tumor-specific T cell responses to epithelial cancers in a personalized manner. We demonstrate that co-cultures of autologous tumor organoids and peripheral blood lymphocytes can be used to enrich tumor-reactive T cells from peripheral blood of patients with mismatch repair-deficient colorectal cancer and non-small-cell lung cancer. Furthermore, we demonstrate that these T cells can be used to assess the efficiency of killing of matched tumor organoids. This platform provides an unbiased strategy for the isolation of tumor-reactive T cells and provides a means by which to assess the sensitivity of tumor cells to T cell-mediated attack at the level of the individual patient.

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Section: Discussionmentioning

confidence: 99%

Generation of Tumor-Reactive T Cells by Co-culture of Peripheral Blood Lymphocytes and Tumor Organoids

Dijkstra

Cattaneo

Weeber

et al. 2018

Cell

775

711

View full text Add to dashboard Cite

show abstract

“…Antitumor immunotherapies using ICIs target T‐cell‐negative feedback loops, augmenting the immune response to attack cancer cells . However, unwanted consequences of their mechanisms of action lead to a unique spectrum of adverse events, most of which are immune‐related adverse events (irAEs) .…”

Section: Introductionmentioning

confidence: 99%

Immune checkpoint inhibitor‐associated pituitary‐adrenal dysfunction: A systematic review and meta‐analysis

Lü

Lan

et al. 2019

Cancer Medicine

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With the growing use of immune checkpoint inhibitors (ICIs), case reports of rare yet life‐threatening pituitary‐adrenal dysfunctions, particularly for hypopituitarism, are increasingly being published. In this analysis, we focus on these events by including the most recent publications and reports from early phase I/II and phase III clinical trials and comparing the incidence and risks across different ICI regimens. PubMed, Embase, and the Cochrane Library were systematically searched from inception to April 2019 for clinical trials that reported on pituitary‐adrenal dysfunction. The rates of events, odds ratios (ORs), and 95% confidence intervals (CIs) were obtained using random effects meta‐analysis. The analyses included data from 160 trials involving 40 432 participants. The rate was 2.43% (95% CI, 1.73%‐3.22%) for all‐grade adrenal insufficiency and 3.25% (95% CI, 2.15%‐4.51%) for hypophysitis. Compared with the placebo or other therapeutic regimens, ICI agents were associated with a higher incidence of serious‐grade adrenal insufficiency (OR 3.19, 95% CI, 1.84 to 5.54) and hypophysitis (OR 4.77, 95% CI, 2.60 to 8.78). Among 71 serious‐grade hypopituitarism instances in 12 336 patients, there was a significant association between ICIs and hypopituitarism (OR 3.62, 95% CI, 1.86 to 7.03). Substantial heterogeneity was noted across the studies for the rates of these events, which in part was attributable to the different types of ICIs and varied phases of the clinical trials. Although the rates of these events were low, the risk was increased following ICI‐based treatment, particularly for CTLA‐4 inhibitors, which were associated with a higher incidence of pituitary‐adrenal dysfunction than PD‐1/PD‐L1 inhibitors.

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“…1,4 Immune checkpoint inhibitors are monoclonal antibodies that could refresh the inactive T cells and unleash durable antitumoral responses by blocking various immune checkpoints, such as cytotoxic T cell lymphocyte-associated protein 4 (CTLA-4), and programmed death receptor 1 (PD-1) and its ligand, known as programmed death receptor ligand 1 (PD-L1). [1][2][3][4] Currently, six monoclonal antibodies targeting checkpoints have been approved by the United States Food and Drug Administration (FDA). 18 The approved indications for these novel agents are described in Table 1.…”

Section: Immune Checkpoint Blockade: a New "Activator" In Cancer Immentioning

confidence: 99%

“…In recent years, tremendous progresses have been achieved in cancer immunotherapy since the introduction of immune checkpoint blockade (ICB) to oncological practice. [1][2][3] Immune checkpoint blockade represents a range of anticheckpoint monoclonal antibodies that could yield remarkable and durable anticancer responses (eg, overall survival [OS] >3 years). [4][5][6][7] Nevertheless, the response rate of ICB varies across diverse tumor types.…”

Section: Introductionmentioning

confidence: 99%

Role of medical imaging for immune checkpoint blockade therapy: From response assessment to prognosis prediction

2019

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Immune checkpoint blockade (ICB) represents a promising approach in cancer therapy. Owing to the peculiar biologic mechanisms of anticancer activity, checkpoint blockers are accompanied with distinctive response patterns and toxicity profiles. Medical imaging is the cornerstone for response assessment to immunotherapy and plays a critical role in monitoring of immune‐related adverse events (irAEs). Imaging‐based biomarkers have shown tremendous potential for the prediction of therapeutic efficacies and clinical outcomes in patients treated with checkpoint inhibitors. In this article, the landscape of current response assessment systems for immunotherapy was reviewed with a special focus on the latest advances in the assessment of responses to ICB. Emerging imaging biomarkers were discussed along with the challenges regarding their clinical transformation. In addition, the biological mechanisms and clinical applications of ICB and irAEs were also within the scope of this review.

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Combination Cancer Therapy with Immune Checkpoint Blockade: Mechanisms and Strategies

Cited by 471 publications

References 174 publications

Generation of Tumor-Reactive T Cells by Co-culture of Peripheral Blood Lymphocytes and Tumor Organoids

Generation of Tumor-Reactive T Cells by Co-culture of Peripheral Blood Lymphocytes and Tumor Organoids

Immune checkpoint inhibitor‐associated pituitary‐adrenal dysfunction: A systematic review and meta‐analysis

Role of medical imaging for immune checkpoint blockade therapy: From response assessment to prognosis prediction

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