Quantitative Spatial Profiling of PD-1/PD-L1 Interaction and HLA-DR/IDO-1 Predicts Improved Outcomes of Anti–PD-1 Therapies in Metastatic Melanoma

Johnson, Douglas B.; Bordeaux, Jennifer; Kim, Ju‐Young; Vaupel, Christine; Rimm, David L.; Ho, Thai H.; Joseph, Richard W.; Daud, Adil; Conry, Robert M.; Gaughan, Elizabeth M.; Hernandez‐Aya, Leonel F.; Dimou, Anastasios; Funchain, Pauline; Smithy, James W.; Witte, John S.; McKee, Svetlana B.; Ko, Jennifer S.; Wrangle, John; Dabbas, Bashar; Tangri, Shabnam; Lameh, Jelveh; Hall, Jeffrey M.; Markowitz, Joseph; Balko, Justin M.; Dakappagari, Naveen

doi:10.1158/1078-0432.ccr-18-0309

Cited by 123 publications

(130 citation statements)

References 38 publications

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“…The impact of PD-L2 expression as a predictive biomarker for anti-PD-1 blockade is not well understood at this time but is currently being explored by a number of investigative groups. Additional features of the PD-1/PD-L1 interaction in pretreatment specimens, such as CD8 density, 34 levels of PD-L1 expression, 75 and PD-1–PD-L1 interaction, 76 may have added value beyond the determination of whether PD-L1 is simply present or absent.…”

Section: Melanoma and Other Cutaneous Malignanciesmentioning

confidence: 99%

Implications of the tumor immune microenvironment for staging and therapeutics

et al. 2018

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Characterizing the tumor immune microenvironment enables the identification of new prognostic and predictive biomarkers, the development of novel therapeutic targets and strategies, and the possibility to guide first-line treatment algorithms. Although the driving elements within the tumor microenvironment of individual primary organ sites differ, many of the salient features remain the same. The presence of a robust antitumor milieu characterized by an abundance of CD8+ cytotoxic T-cells, Th1 helper cells, and associated cytokines often indicates a degree of tumor containment by the immune system and can even lead to tumor elimination. Some of these features have been combined into an ‘Immunoscore’, which has been shown to complement the prognostic ability of the current TNM staging for early stage colorectal carcinomas. Features of the immune microenvironment are also potential therapeutic targets, and immune checkpoint inhibitors targeting the PD-1/ PD-L1 axis are especially promising. FDA-approved indications for anti-PD-1/PD-L1 are rapidly expanding across numerous tumor types and, in certain cases, are accompanied by companion or complimentary PD-L1 immunohistochemical diagnostics. Pathologists have direct visual access to tumor tissue and in-depth knowledge of the histological variations between and within tumor types and thus are poised to drive forward our understanding of the tumor microenvironment. This review summarizes the key components of the tumor microenvironment, presents an overview of and the challenges with PD-L1 antibodies and assays, and addresses newer candidate biomarkers, such as CD8+ cell density and mutational load. Characteristics of the local immune contexture and current pathology-related practices for specific tumor types are also addressed. In the future, characterization of the host antitumor immune response using multiplexed and multimodality biomarkers may help predict which patients will respond to immune-based therapies.

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Section: Melanoma and Other Cutaneous Malignanciesmentioning

confidence: 99%

Implications of the tumor immune microenvironment for staging and therapeutics

et al. 2018

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“…The recent development of another multiplex technology, TSA‐based mIHC/IF such as Vectra (Akoya Bioscience, Menlo Park, California, USA; Figure 1C), may resolve some of the issues with the use of other mIHC/IF systems. This method allows simultaneous antibody‐based detection and quantification of the expression of up to six protein markers (recently 9 or more markers) [4, 72, 5, 3, 29, 73], plus a nuclear counterstain, on a single tissue section. This provides the opportunity and possibility to acquire gold‐standard diagnostic and prognostic information.…”

Section: Brightfield‐based Mihc/ifmentioning

confidence: 99%

“…The Vectra system is the most widely adopted mIHC/IF system currently with several notable publications [4, 72, 5, 3, 29, 73, 81, 82] over the past half a decade worldwide. Some institutions and hospitals even utilize this technology as part of their clinical laboratory tests to help clinicians in their clinical decision making and treatment plans.…”

Section: Brightfield‐based Mihc/ifmentioning

confidence: 99%

“…[1] published a meta‐analysis of different strategies for predicting response to anti PD1/PDL1 treatment which adopted multiple studies of TSA‐based mIHC/IF assays. These studies evaluated parameters such as PD‐1 to PD‐L1 proximity [73, 75], CD8 + cell density within a specific TME compartment (for instance: intratumoral/peritumoral defined by IHC/IF tumor marker [23, 29]), or co‐expressed markers indicating T‐cell activation [49, 111] as summarized in Table 3. For instance, Johnson et al .…”

Section: Brightfield‐based Mihc/ifmentioning

confidence: 99%

“…For instance, Johnson et al . [112] and Giraldo et al. [113] evaluated PD‐1 to PD‐L1 proximity using TSA‐based mIHC/IF in metastatic melanoma in 166 patients and Merkel cell carcinoma in 42 patients, respectively.…”

Section: Brightfield‐based Mihc/ifmentioning

confidence: 99%

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Overview of multiplex immunohistochemistry/immunofluorescence techniques in the era of cancer immunotherapy

Tan

Nerurkar

Cai

et al. 2020

Cancer Communications

366

318

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Conventional immunohistochemistry (IHC) is a widely used diagnostic technique in tissue pathology. However, this technique is associated with a number of limitations, including high inter-observer variability and the capacity to label only one marker per tissue section. This review details various highly multiplexed techniques that have emerged to circumvent these constraints, allowing simultaneous detection of multiple markers on a single tissue section and the comprehensive study of cell composition, cellular functional and cell-cell interactions. Among these techniques, multiplex Immunohistochemistry/Immunofluorescence (mIHC/IF) has emerged to be particularly promising. mIHC/IF provides high-throughput multiplex staining and standardized quantitative analysis for highly reproducible, efficient and cost-effective tissue studies. This technique has immediate potential for translational research and clinical practice, particularly in the era of cancer immunotherapy.

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Comparison of Biomarker Modalities for Predicting Response to PD-1/PD-L1 Checkpoint Blockade

et al. 2019

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IMPORTANCE PD-L1 (programmed cell death ligand 1) immunohistochemistry (IHC), tumor mutational burden (TMB), gene expression profiling (GEP), and multiplex immunohistochemistry/immunofluorescence (mIHC/IF) assays have been used to assess pretreatment tumor tissue to predict response to anti-PD-1/PD-L1 therapies. However, the relative diagnostic performance of these modalities has yet to be established.OBJECTIVE To compare studies that assessed the diagnostic accuracy of PD-L1 IHC, TMB, GEP, and mIHC/IF in predicting response to anti-PD-1/PD-L1 therapy.

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Quantitative Spatial Profiling of PD-1/PD-L1 Interaction and HLA-DR/IDO-1 Predicts Improved Outcomes of Anti–PD-1 Therapies in Metastatic Melanoma

Cited by 123 publications

References 38 publications

Implications of the tumor immune microenvironment for staging and therapeutics

Implications of the tumor immune microenvironment for staging and therapeutics

Overview of multiplex immunohistochemistry/immunofluorescence techniques in the era of cancer immunotherapy

Comparison of Biomarker Modalities for Predicting Response to PD-1/PD-L1 Checkpoint Blockade

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