Research

Impact of genetic aberrations on the Tumor Microenvironment (TME)

We aim to investigate how genetic aberrations in cancer cells influence the composition and functional state of the Tumor Microenvironment (TME). Such aberrations may affect the recruitment, abundance, or activation state of various cell types within the TME, ultimately shaping the tumor’s immunogenicity. For instance, certain genetic changes can promote infiltration by Tumor-Infiltrating Lymphocytes (TILs), resulting in so-called “hot” tumors, which are recognized and targeted by the immune system. In contrast, “cold” tumors lack significant immune cell infiltration and remain largely undetected by the host’s immune response. These differences are clinically relevant, as patients with hot tumors generally experience better outcomes and may respond more favourably to immunotherapies.

TILs are associated with a deletion of 13q14.2 in UPS (Sarcoma). Samples were split into three equally sized groups based on their TIL score. The oncoprint shows deletions, fusions and SNVs enriched in the lower TIL score tertile for UPS. Additionally, the bottom heatmaps show matched gene expression data. The tumor suppressor gene RB1 was deleted in seven out of 15 samples belonging to the low TIL group.

Relevant publications:

Deconvolution of sarcoma methylomes reveals varying degrees of immune cell infiltrates with association to genomic aberrations

J Transl Med. 2022 Apr 2;20(1):152. doi: 10.1186/s12967-021-02858-7

Chronic Chromosome Instability Induced by Plk1 Results in Immune Suppression in Breast Cancer

Cell Reports. 2023 Dec 26;42(12):113266. doi: 10.1186/s12967-021-02858-7

Leveraging TCRs to Understand T Cell Clonality Dynamics in Health and Disease

T Cell Receptors (TCRs) provide a unique molecular barcode, enabling us to track individual T cell clones across time, tissues, and disease states. By analyzing TCR repertoires, we uncover how T cells expand, persist, and adapt—whether in response to infection, within the tumor microenvironment, or following vaccination. Our research aims to decode these clonality dynamics to better understand immune activation and to map T cell migration across tissues and circulation.

Relevant publications:

Precursors for Nonlymphoid-Tissue Treg Cells Reside in Secondary Lymphoid Organs and Are Programmed by the Transcription Factor BATF

J Transl Med. 2022 Apr 2;20Immunity. 2020 Feb 18;52(2):295-312.e11. doi: 10.1016/j.immuni.2019.12.002