Last updated: 2021-08-04
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Knit directory: MelanomaIMC/
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| File | Version | Author | Date | Message |
|---|---|---|---|---|
| html | e9a4766 | toobiwankenobi | 2021-07-07 | adapt |
| Rmd | ee1595d | toobiwankenobi | 2021-02-12 | clean repo and adapt files |
| html | ee1595d | toobiwankenobi | 2021-02-12 | clean repo and adapt files |
| html | 2e443a5 | toobiwankenobi | 2021-02-09 | remove files that are not needed |
| 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. |
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: daniel.schulz@uzh.ch bernd.bodenmiller@uzh.ch
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.