Kliniken &… Kliniken Hautklinik… Hauttumorzentrum Forschung AG Reschke (Max-Eder…

AG RESCHKE - MAX-EDER JUNIOR RESEARCH GROUP

Microbiome-induced T cells as potential therapeutic targets for unresectable or metastasized skin cancer

Previous and current research

Immunotherapy has revolutionized the treatment of cancer. Checkpoint blocking antibodies have been Food and Drug Administration (FDA)-approved for a multitude of cancer types, unresectable or metastatic cutaneous squamous cell carcinoma (cSCC) among these. However, a majority of patients do not benefit from immunotherapy and they succumb to metastatic cancer. 

Recently, tissue resident memory T (TRM) cells have been implicated in a variety of solid tumors as prognostically beneficial for immunotherapy. In the context of immune-related adverse events we have shown that TRM cells exhibit strong expression of inhibitory checkpoint molecules, such as PD-1, CTLA-4 and LAG-3, leading us to propose that they expand during immunotherapy. TRM cells can produce IFN-γ which induces production CXCL9/10/11 by surrounding cells such as myeloid cells. These chemokines can recruit additional tumor infiltrating effector T cells (TILs) from the blood stream by binding to the CXCR3 receptor on the surface of T cells. 

A potential reason for accumulation of TRM in the skin in the first place could be exposure to microbial peptides that serve as antigens. The present project aims to decode the link between cutaneous microbiome and TRM formation. Clinical response data from patients receiving immunotherapy will be linked to multi-omics data from patient specimen. Addressing these questions, we will use cutting-edge spatial technologies (see figure below) on samples from cSCCs and other skin cancers.

The overall goal is to identify mechanism-based biomarkers or novel target molecules that expand efficacy of immunotherapy to non-response patients across solid tumors.

Group Leader

Team

Recruiting MD and PhD students eager to work in a lab that tries to understand and improve immunotherapy across cancers! Interested in working at the intersection of dermatology, oncology, immunology and microbiology? 

Reach out to robinniklas.reschke(at)med.uni-heidelberg.de with your CV and references. 

Reschke R, Shapiro JW, Yu J, Rouhani SJ, Olson DJ, Zha Y, et al. Checkpoint blockade–induced dermatitis and colitis are dominated by tissue resident memory T cells and Th1/Tc1 cytokines. Cancer Immunology Research 2022:CIR-22-0362. https://doi.org/10.1158/2326-6066.CIR-22-0362

Reschke R, Gajewski TF. CXCL9 and CXCL10 bring the heat to tumors. Science Immunology 2022;7:eabq6509. https://doi.org/10.1126/sciimmunol.abq6509

Reschke R, Yu J, Flood BA, Higgs EF, Hatogai K, Gajewski TF. Immune cell and tumor cell-derived CXCL10 is indicative of immunotherapy response in metastatic melanoma. J Immunother Cancer 2021;9:e003521. https://doi.org/10.1136/jitc-2021-003521

Reschke R, Deitert B, Enk AH, Hassel JC. The role of tissue-resident memory T cells as mediators for response and toxicity in immunotherapy-treated melanoma-two sides of the same coin? Front Immunol. 2024 Mar 18;15:1385781. https://doi.org/10.3389/fimmu.2024.1385781

Reschke R, Gussek P, Boldt A, Sack U, Köhl U, Lordick F, Gora T, Kreuz M, Reiche K, Simon JC, Ziemer M, Kunz M. Distinct Immune Signatures Indicative of Treatment Response and Immune-Related Adverse Events in Melanoma Patients under Immune Checkpoint Inhibitor Therapy. Int J Mol Sci. 2021 Jul 27;22(15):8017. https://doi.org/10.3390/ijms22158017

Reschke R, Gussek P, Ziemer M. Identifying High-Risk Tumors within AJCC Stage IB-III Melanomas Using a Seven-Marker Immunohistochemical Signature. Cancers (Basel). 2021 Jun 10;13(12):2902. https://doi.org/10.3390/cancers13122902

Reschke R, Olson DJ. Leveraging STING, Batf3 Dendritic Cells, CXCR3 Ligands, and Other Components Related to Innate Immunity to Induce A "Hot" Tumor Microenvironment That Is Responsive to Immunotherapy. Cancers (Basel). 2022 May 16;14(10):2458. https://doi.org/10.3390/cancers14102458

Portrait Liban Mahdi
Liban Mahdi

MD student (Hauttumorzentrum Heidelberg)