Last updated: 2021-11-13

Checks: 2 0

Knit directory: MelanomaIMC/

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html 434eee4 toobiwankenobi 2021-09-23 Figure adaptions and new Supp Figure with gates
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html d1c9a41 toobiwankenobi 2021-02-09 index file
html 3828d53 toobiwankenobi 2021-02-09 index file
html c19bae4 toobiwankenobi 2021-02-09 add index file
Rmd f075b06 toobiwankenobi 2020-07-28 Start workflowr project.

Multiplexed Imaging Mass Cytometry in Metastatic Melanoma Utilizing RNA and Protein Co-Detection Links Features of Response to Immunotherapy

Tobias Hoch\(^{1,2,3,5}\), Daniel Schulz\(^{1,2,5,*}\), Nils Eling\(^{1,2}\), Julia Martínez Gómez\(^{4}\), Mitch Levesque\(^{4}\), Bernd Bodenmiller\(^{1,2,*}\)

1 University of Zurich, Department of Quantitative Biomedicine, Zurich, 8057, Switzerland
2 ETH Zurich, Institute for Molecular Health Sciences, Zurich, 8093 Switzerland
3 Particles-Biology Interactions Lab, Empa, Swiss Federal Laboratories for Materials Science and Technology, St. Gallen, 9014, Switzerland
4 University Hospital Zurich, Department of Dermatology, Schlieren, 8952, Switzerland
5 These authors contributed equally
* Correspondence:

Abstract

Intratumoral immune cells are crucial for tumor control and anti-tumor responses during immunotherapy. Immune cell trafficking into tumors is mediated by chemokines, which are expressed and secreted upon various stimuli and interact with specific receptors. To broadly characterize chemokine expression and function in tumors, we have used multiplex mass cytometry-based imaging of protein markers and RNA transcripts to analyze the chemokine landscape and immune infiltration in metastatic melanoma samples. Tumors that lacked immune infiltration were devoid of most chemokines and exhibited particularly low levels of antigen presentation and inflammation. Infiltrated tumors were characterized by expression of multiple chemokines. CXCL9 and CXCL10 were often localized in patches associated with dysfunctional T cells expressing CXCL13 which was strongly associated with B cell patches and follicles. TCF7+ naïve-like T cells, which predict response to immunotherapy, were enriched in the vicinity of B cell patches and follicles. Our data highlight the strength of RNA and protein co-detection which was critical to deconvolve specialized immune microenvironments in inflamed tumors based on chemokine expression. Our findings further suggest that the formation of tertiary lymphoid structures is accompanied by naïve and naive- like T cell recruitment, which ultimately boosts anti-tumor activity.

How-To reproduce the pipeline

  1. Download the data and store the folder (folder name) in MelanomaIMC/data
  2. Download the docker container containing all required packages
  3. Install the docker container following these instructions
  4. Open the RStudio interface following these instructions
  5. Run Files!