Immune signature as predictive marker for response to checkpoint inhibitor immunotherapy and overall survival in melanoma

Krebs, Franziska; Trzeciak, Emily R; Zimmer, S; Özistanbullu, Deniz; Mitzel-Rink, Heidrun; Meißner, Markus; Grabbe, Stephan; Loquai, Carmen; Tuettenberg, Andrea

doi:10.1002/cam4.3710

Cited by 18 publications

(14 citation statements)

References 45 publications

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“…Analysis of peripheral blood mononuclear cells (PBMCs) via flow cytometry, before and during treatment with ipilimumab, indicated that patients with low frequencies of circulating Lin − CD14 + HLA-DR - M-MDSCs showed an improved clinical response to this therapy [ 103 ]. These data confirm similar findings in other studies in metastatic melanoma patients treated with ipilimumab [ 104 , 105 , 106 ]. Current research is focused on identifying a reliable and clinically relevant method to use MDSC frequency as a biomarker for the clinical response to ipilimumab in melanoma patients [ 107 ].…”

Section: Role Of Mdscs In Resistance To Immunotherapeuticssupporting

confidence: 93%

Immunosuppressive Effects of Myeloid-Derived Suppressor Cells in Cancer and Immunotherapy

Krishnamoorthy

Gerhardt

Vareki

2021

Cells

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The primary function of myeloid cells is to protect the host from infections. However, during cancer progression or states of chronic inflammation, these cells develop into myeloid-derived suppressor cells (MDSCs) that play a prominent role in suppressing anti-tumor immunity. Overcoming the suppressive effects of MDSCs is a major hurdle in cancer immunotherapy. Therefore, understanding the mechanisms by which MDSCs promote tumor growth is essential for improving current immunotherapies and developing new ones. This review explores mechanisms by which MDSCs suppress T-cell immunity and how this impacts the efficacy of commonly used immunotherapies.

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Section: Role Of Mdscs In Resistance To Immunotherapeuticssupporting

confidence: 93%

Immunosuppressive Effects of Myeloid-Derived Suppressor Cells in Cancer and Immunotherapy

Krishnamoorthy

Gerhardt

Vareki

2021

Cells

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“…CAP has been widely hailed as a promising anticancer treatment strategy due to its selective targeting of cancer cells [25]. However, relatively little is known about how CAP affects the other cells that make up the melanoma microenvironment, which can greatly influence the therapy outcome [26,27].…”

Section: Cd4 + and Cd8 + T Cells Exhibit A Higher Sensitivity To Cap ...mentioning

confidence: 99%

“…This study also examined the effect of CAP on human monocyte-derived macrophages, another important immune cell type found in the melanoma microenvironment [27]. Resting M0 macrophages were treated with varying amounts of CAP to determine if CAP treatment could affect their viability.…”

Section: Macrophages Are Highly Resistant To Cap and Can Be Polarized...mentioning

confidence: 99%

“…Although the influence of CAP on tumor cells has been extensively studied, relatively little is known regarding how CAP influences the different cells that make up the tumor microenvironment, which can greatly influence therapy response and patient prognosis [26,27]. The present study aimed to address how CAP treatment affects the survival and metabolism of tumor cells, T cells, and macrophages, which, amongst others, compose the melanoma microenvironment.…”

Section: Introductionmentioning

confidence: 99%

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Oxidative Stress Differentially Influences the Survival and Metabolism of Cells in the Melanoma Microenvironment

Trzeciak

Zimmer

Gehringer

et al. 2022

Cells

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The cellular composition of the tumor microenvironment, including tumor, immune, stromal, and endothelial cells, significantly influences responses to cancer therapies. In this study, we analyzed the impact of oxidative stress, induced by cold atmospheric plasma (CAP), on tumor cells, T cells, and macrophages, which comprise part of the melanoma microenvironment. To accomplish this, cells were grown in different in vitro cell culture models and were treated with varying amounts of CAP. Subsequent alterations in viability, proliferation, and phenotype were analyzed via flow cytometry and metabolic alterations by Seahorse Cell Mito Stress Tests. It was found that cells generally exhibited reduced viability and proliferation, stemming from CAP induced G2/M cell cycle arrest and subsequent apoptosis, as well as increased mitochondrial stress following CAP treatment. Overall, sensitivity to CAP treatment was found to be cell type dependent with T cells being the most affected. Interestingly, CAP influenced the polarization of M0 macrophages to a “M0/M2-like” phenotype, and M1 macrophages were found to display a heightened sensitivity to CAP induced mitochondrial stress. CAP also inhibited the growth and killed melanoma cells in 2D and 3D in vitro cell culture models in a dose-dependent manner. Improving our understanding of oxidative stress, mechanisms to manipulate it, and its implications for the tumor microenvironment may help in the discovery of new therapeutic targets.

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“…Whereas the treatment success with checkpoint inhibitors, especially in melanoma, has been ground-breaking both for progression-free and overall survival, only part of the patients show a good response, whereas others do not benefit from this treatment. Many efforts are made to investigate biomarkers to identify and characterize parameters in peripheral blood or tumor microenvironment from melanoma patients to solve this question [19]. In the present study, we investigated immunophenotyping of melanoma, and report on its comparison to flow cytometry and IHC in a relevant preclinical humanized mouse model of melanoma.…”

Section: Introductionmentioning

confidence: 99%

In-Depth Immune-Oncology Studies of the Tumor Microenvironment in a Humanized Melanoma Mouse Model

Schupp

Christians²,

Zimmer

et al. 2021

IJMS

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The presence and interaction of immune cells in the tumor microenvironment is of significant importance and has a great impact on disease progression and response to therapy. Hence, their identification is of high interest for prognosis and treatment decisions. Besides detailed phenotypic analyses of immune, as well as tumor cells, spatial analyses is an important parameter in the complex interplay of neoplastic and immune cells—especially when moving into focus efforts to develop and validate new therapeutic strategies. Ex vivo analysis of tumor samples by immunohistochemistry staining methods conserves spatial information is restricted to single markers, while flow cytometry (disrupting tissue into single cell suspensions) provides access to markers in larger numbers. Nevertheless, this comes at the cost of scarifying morphological information regarding tissue localization and cell–cell contacts. Further detrimental effects incurred by, for example, tissue digestion include staining artifacts. Consequently, ongoing efforts are directed towards methods that preserve, completely or in part, spatial information, while increasing the number of markers that can potentially be interrogated to the level of conventional flow cytometric methods. Progression in multiplex immunohistochemistry in the last ten years overcame the limitation to 1–2 markers in classical staining methods using DAB with counter stains or even pure chemical staining methods. In this study, we compared the multiplex method Chipcytometry to flow cytometry and classical IHC-P using DAB and hematoxylin. Chipcytometry uses frozen or paraffin-embedded tissue sections stained with readily available commercial fluorophore-labeled antibodies in repetitive cycles of staining and bleaching. The iterative staining approach enables sequential analysis of a virtually unlimited number of markers on the same sample, thereby identifying immune cell subpopulations in the tumor microenvironment in the present study in a humanized mouse melanoma model.

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Immune signature as predictive marker for response to checkpoint inhibitor immunotherapy and overall survival in melanoma

Cited by 18 publications

References 45 publications

Immunosuppressive Effects of Myeloid-Derived Suppressor Cells in Cancer and Immunotherapy

Immunosuppressive Effects of Myeloid-Derived Suppressor Cells in Cancer and Immunotherapy

Oxidative Stress Differentially Influences the Survival and Metabolism of Cells in the Melanoma Microenvironment

In-Depth Immune-Oncology Studies of the Tumor Microenvironment in a Humanized Melanoma Mouse Model

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