Polygenic risk for skin autoimmunity impacts immune checkpoint blockade in bladder cancer

Khan, Zia; Nucci, Flavia Di; Kwan, Antonia; Hammer, Christian; Mariathasan, Sanjeev; Rouilly, Vincent; Carroll, Jonathan; Fontes, Magnus; Acosta, Sergio Ley; Guardino, Ellie; Chen-Harris, Haiyin; Bhangale, Tushar; Mellman, Ira; Rosenberg, Jacob; Powles, Thomas; Hunkapiller, Julie; Chandler, G. Scott; Albert, Matthew L.

doi:10.1073/pnas.1922867117

Cited by 71 publications

(48 citation statements)

References 27 publications

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“…In addition to these two studies, Khan et al. recently published a retrospective analysis of clinical trial data of 220 bladder cancer patients ( 36 ). By means of whole genome sequencing they calculated polygenic risk scores for skin autoimmunity and found that psoriasis-associated polygenic risk scores were correlated to dermal irAE development (p < 0.05).…”

Section: Biomarkersmentioning

confidence: 99%

Biomarkers of Checkpoint Inhibitor Induced Immune-Related Adverse Events—A Comprehensive Review

et al. 2021

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Immune checkpoint inhibitors (ICIs) have substantially improved the prognosis of patients with different types of cancer. Through blockade of cytotoxic T-lymphocyte antigen 4 (CTLA-4) and programmed cell death protein 1 (PD-1), negative feedback mechanisms of the immune system are inhibited, potentially resulting in very durable anti-tumor responses. Despite their promise, ICIs can also elicit auto-immune toxicities. These immune-related adverse events (irAEs) can be severe and sometimes even fatal. Therefore, being able to predict severe irAEs in patients would be of added value in clinical decision making. A search was performed using “adverse events”, “immune checkpoint inhibitor”, “biomarker”, and synonyms in PubMed, yielding 3580 search results. After screening title and abstract on the relevance to the review question, statistical significance of reported potential biomarkers, and evaluation of the remaining full papers, 35 articles were included. Five additional reports were obtained by means of citations and by using the similar article function on PubMed. The current knowledge is presented in comprehensive tables summarizing blood-based, immunogenetic and microbial biomarkers predicting irAEs prior to and during ICI therapy. Until now, no single biomarker has proven to be sufficiently predictive for irAE development. Recommendations for further research on this topic are presented.

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Section: Biomarkersmentioning

confidence: 99%

Biomarkers of Checkpoint Inhibitor Induced Immune-Related Adverse Events—A Comprehensive Review

et al. 2021

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“…For example, Arbour et al reported that baseline GC equivalent to more than 10 mg prednisolone per day was associated with significantly poorer overall survival on multivariate analysis in patients with NSCLC (hazard ratio, 1.66; p < .001) [48]. Genetic variants partly explain the risk of autoimmune conditions that are treated with systemic steroids, such as RA [51], and in turn, such variants are associated with enhanced responsiveness to ICI [52]. This potentially confounding issue may partly explain contradictory findings regarding the association between baseline GC and ICI response, which has not been consistently demonstrated in all patient cohorts [53].…”

Section: Clinical Studies Relating To Coadministration Of Glucocorticmentioning

confidence: 99%

Reconsidering Dexamethasone for Antiemesis when Combining Chemotherapy and Immunotherapy

2021

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Whether the immune suppressive action of glucocorticoid steroids, such as dexamethasone, might reduce the benefits of cancer immunotherapy has long been a concern. Observations that established tumor regressions in response to immune checkpoint inhibitors (ICIs) often persist, despite the use of steroids to mitigate ICI‐related autoimmune breakthrough, are not sufficiently reassuring, because these observations do not address the potential blunting of immune priming at the initiation of ICI therapy. With increasing indications for ICI in combination with chemotherapy, this issue merits reconsideration. Professional society guidance advises that dexamethasone should be used as first‐line prophylaxis for nausea and vomiting in patients receiving ICI and highly emetogenic chemotherapy combination regimens. Here, we review the availability of data on this subject and propose an alternative approach focused on the adoption of steroid minimization or sparing for prophylaxis of nausea until the underlying immune biology is better understood.

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“…2-Deoxy-2-(18F)fluoro- D -glucose positron emission tomography/computed tomography performed during the treatment for restaging and/or response assessment can also reveal a wide range of IrAEs, (e.g., sarcoidosis-like syndrome, thyroiditis, hypophysitis, enterocolitis, interstitial pneumonitis, pancreatitis, and arthritis) with an accuracy of 83% ( 58 , 59 ). Authors recently reported that shared genetic factors impact risk for IrAEs and survival on immunotherapy in BC ( 60 ).…”

Section: Response Evaluationmentioning

confidence: 99%

The Role of 18F-FDG PET/CT in Guiding Precision Medicine for Invasive Bladder Carcinoma

et al. 2020

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Bladder cancer (BC) is the 10th most common cancer worldwide. Approximately one quarter of patients with BC have muscle-invasive disease (MIBC). Muscle-invasive disease carries a poor prognosis and choosing the optimal treatment option is critical to improve patients’ outcomes. Ongoing research supports the role of 2-deoxy-2-(18F)fluoro- D -glucose positron emission tomography (18F-FDG PET) in guiding patient-specific management decisions throughout the course of MIBC. As an imaging modality, 18F-FDG PET is acquired simultaneously with either computed tomography (CT) or MRI to offer a hybrid approach combining anatomical and metabolic information that complement each other. At initial staging, 18F-FDG PET/CT enhances the detection of extravesical disease, particularly in patients classified as oligometastatic by conventional imaging. 18F-FDG PET/CT has value in monitoring response to neoadjuvant and systemic chemotherapy, as well as in localizing relapse after treatment. In the new era of immunotherapy, 18F-FDG PET/CT may also be useful to monitor treatment efficacy as well as to detect immune-related adverse events. With the advent of artificial intelligence techniques such as radiomics and deep learning, these hybrid medical images can be mined for quantitative data, providing incremental value over current standard-of-care clinical and biological data. This approach has the potential to produce a major paradigm shift toward data-driven precision medicine with the ultimate goal of personalized medicine. In this review, we highlight current literature reporting the role of 18F-FDG PET in supporting personalized management decisions for patients with MIBC. Specific topics reviewed include the incremental value of 18F-FDG PET in prognostication, pre-operative planning, response assessment, prediction of recurrence, and diagnosing drug toxicity.

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Polygenic risk for skin autoimmunity impacts immune checkpoint blockade in bladder cancer

Cited by 71 publications

References 27 publications

Biomarkers of Checkpoint Inhibitor Induced Immune-Related Adverse Events—A Comprehensive Review

Biomarkers of Checkpoint Inhibitor Induced Immune-Related Adverse Events—A Comprehensive Review

Reconsidering Dexamethasone for Antiemesis when Combining Chemotherapy and Immunotherapy

The Role of 18F-FDG PET/CT in Guiding Precision Medicine for Invasive Bladder Carcinoma

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