A total of 104 patients with recurrent/metastatic SGC from the DKTK MASTER program were included in this study. Whole-exome or whole-genome sequencing and RNA-sequencing was performed on fresh frozen tumor tissue. The tumor immune microenvironment was analyzed using CIBERSORT deconvolution analysis and immune gene expression scores in bulk RNA-sequencing data. Single-nuclei sequencing and immunohistochemistry analyses were performed in selected samples. Results were validated in bulk RNA-sequencing data of a previously published independent dataset.

CH received honoraria, research funding and/or consulting/advisory board from Roche, Novartis, Boehringer Ingelheim. SF has had a consulting or advisory role and received honoraria, research funding, and/or travel/accommodation expenses funding from the following for-profit companies: Amgen, AstraZeneca, Bayer, Eli Lilly, Pfizer, PharmaMar, and Roche. DTR has received honoraria, research support and/or travel/accommodation expenses from Bayer, Eli Lilly, Bristol-Myers Squibb, Roche and Seagen.

The MASTER program is supported by the NCT Molecular Precision Oncology Program, DKFZ, and DKTK. This project was supported by the Deutsche Forschungsgemeinschaft (No. RTG2424 CompCancer, EZ) and a Berlin Institute of Health Booster Grant (EZ, DB, DTR). DTR is a participant in the Berlin Institute of Health −- Charité Clinical Scientist Program funded by the Charité − Universitaetsmedizin Berlin and the Berlin Institute of Health. Part of this work was supported by the ACC Research Foundation (DTR).

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The DKTK MASTER program was approved by ethics committees at all participating sites (Lead Heidelberg, S-206/2011). Written informed consent was obtained from all participants. Ethics approval for retrospective analysis of tumor samples from patients not participating in the DKTK MASTER program was obtained separately (Berlin, EA1/305/21).

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

Yes

I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes

The datasets generated and/or analysed during the current study are not publicly available due to missing approval by participating patients but are available from the corresponding author on reasonable request.