PD-L1 Copy Number Variation Does Not Correlate With PD-L1 Expression or Response to Anti-PD-1 Immunotherapy In Patients With Advanced Melanomas

Pérottet, Jérémy; Goff, Emeline Le; Legoupil, Délphine; Quéré, Gilles; Schick, Ulrike; Marcorelles, Pascale; Uguen, Arnaud

doi:10.1097/pai.0000000000000712

Cited by 10 publications

(9 citation statements)

References 20 publications

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“…As more immunotherapies are developed and approved, researchers have sought to use FISH to predict responsiveness to immunotherapy in cancer. Not surprisingly, PD-L1 status is commonly investigated but its predictive and prognostic value are variable [ 34 , 35 , 36 ]. In addition, FISH might be useful for predicting responsiveness to intravesical bacillus Calmette–Guerin immunotherapy in bladder cancer [ 37 , 38 ].…”

Section: In Situ Hybridizationmentioning

confidence: 99%

Transcriptional Spatial Profiling of Cancer Tissues in the Era of Immunotherapy: The Potential and Promise

Nerurkar

Goh

Cheung

et al. 2020

Cancers

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Intratumoral heterogeneity poses a major challenge to making an accurate diagnosis and establishing personalized treatment strategies for cancer patients. Moreover, this heterogeneity might underlie treatment resistance, disease progression, and cancer relapse. For example, while immunotherapies can confer a high success rate, selective pressures coupled with dynamic evolution within a tumour can drive the emergence of drug-resistant clones that allow tumours to persist in certain patients. To improve immunotherapy efficacy, researchers have used transcriptional spatial profiling techniques to identify and subsequently block the source of tumour heterogeneity. In this review, we describe and assess the different technologies available for such profiling within a cancer tissue. We first outline two well-known approaches, in situ hybridization and digital spatial profiling. Then, we highlight the features of an emerging technology known as Visium Spatial Gene Expression Solution. Visium generates quantitative gene expression data and maps them to the tissue architecture. By retaining spatial information, we are well positioned to identify novel biomarkers and perform computational analyses that might inform on novel combinatorial immunotherapies.

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Section: In Situ Hybridizationmentioning

confidence: 99%

Transcriptional Spatial Profiling of Cancer Tissues in the Era of Immunotherapy: The Potential and Promise

Nerurkar

Goh

Cheung

et al. 2020

Cancers

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“…This compares favourably to the matched cohort response rate of 29.8% (45/151, P = .03) and, despite the small subsets, this urges further investigation into PD‐L1 CNA amplification prospectively 146 . Retrospective analysis of tumour samples in patients with metastatic melanoma using IHC and PD‐L1/9p24 FISH to detect PD‐L1 (note not assessing PD‐L2) CNA showed no predictive potential of IHC or FISH for response to ICBs, 147 urging caution at current use of PD‐L1/2 CNA to guide clinical decision‐making at present.…”

Section: Genotypic Predictors Of Responsementioning

confidence: 88%

Immune checkpoint blockade in solid organ tumours: Choice, dose and predictors of response

Navani

Graves

Westhuizen

2020

Brit J Clinical Pharma

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Immune checkpoint blockade has transformed outcomes across solid organ tumours. Monoclonal antibodies targeting the negative inhibitory cytotoxic T lymphocyte‐associated protein 4 and programmed‐death 1/programmed death‐ligand 1 axis can lead to deep and durable responses across several tumour streams in the advanced setting. This immunotherapy approach is increasingly used earlier in the treatment paradigm. A rapidly evolving regulatory, reimbursement and drug development landscape has accompanied this novel class of immunotherapy. Unfortunately, only a small proportion of patients respond meaningfully to these agents. Here we review how the underlying tumoural genomic, histological and immunological characteristics interact within various patient phenotypes, leading to variations in response to checkpoint blockade. Concurrently, we outline the clinical trial and real‐world evidence that allows for appropriate selection of agent, dose and schedule in solid organ malignancies. An exploration of current trends in basic and translational research in immune checkpoint blockade accompanies a commentary on future clinical directions for checkpoint blockade in oncology.

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“…Many mutations, such as the BCR-ABL1 t (9; 22) translocation, EML4-ALK fusion gene and TMPRSS2-ERG fusion gene, have been identified by FISH in chronic myeloid leukemia, non-small cell lung cancer and prostate cancer, respectively ( 67 , 100 , 101 ). Researchers have also used FISH to predict and judge the clinical response to PD-1 blockade therapy in advanced melanomas and renal cell carcinomas ( 102 , 103 ). By overcoming the limitation of conventional FISH at the DNA level, RNAscope was developed to detect low-content mRNA, avoiding high background, and applied in evaluating the expression of immune checkpoints in cancers for diagnosis, including lung adenosquamous cell carcinomas, advanced gastric cancer, triple-negative breast cancer and bladder carcinomas ( 104 – 107 ).…”

Section: Spatial Profiling Technologies Applicationsmentioning

confidence: 99%

A review of spatial profiling technologies for characterizing the tumor microenvironment in immuno-oncology

Sajid

Rong

et al. 2022

Front. Immunol.

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Interpreting the mechanisms and principles that govern gene activity and how these genes work according to -their cellular distribution in organisms has profound implications for cancer research. The latest technological advancements, such as imaging-based approaches and next-generation single-cell sequencing technologies, have established a platform for spatial transcriptomics to systematically quantify the expression of all or most genes in the entire tumor microenvironment and explore an array of disease milieus, particularly in tumors. Spatial profiling technologies permit the study of transcriptional activity at the spatial or single-cell level. This multidimensional classification of the transcriptomic and proteomic signatures of tumors, especially the associated immune and stromal cells, facilitates evaluation of tumor heterogeneity, details of the evolutionary trajectory of each tumor, and multifaceted interactions between each tumor cell and its microenvironment. Therefore, spatial profiling technologies may provide abundant and high-resolution information required for the description of clinical-related features in immuno-oncology. From this perspective, the present review will highlight the importance of spatial transcriptomic and spatial proteomics analysis along with the joint use of other sequencing technologies and their implications in cancers and immune-oncology. In the near future, advances in spatial profiling technologies will undoubtedly expand our understanding of tumor biology and highlight possible precision therapeutic targets for cancer patients.

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PD-L1 Copy Number Variation Does Not Correlate With PD-L1 Expression or Response to Anti-PD-1 Immunotherapy In Patients With Advanced Melanomas

Cited by 10 publications

References 20 publications

Transcriptional Spatial Profiling of Cancer Tissues in the Era of Immunotherapy: The Potential and Promise

Transcriptional Spatial Profiling of Cancer Tissues in the Era of Immunotherapy: The Potential and Promise

Immune checkpoint blockade in solid organ tumours: Choice, dose and predictors of response

A review of spatial profiling technologies for characterizing the tumor microenvironment in immuno-oncology

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