Center for Molecular Medicine Cologne

Hans A Schlößer - CAP 12

Tumor-specific endogenous immune response and immune escape in gastrointestinal Cancer

Introduction

Immune checkpoint inhibition (CKI) demonstrated remarkable efficacy in several kinds of cancer, representing a major breakthrough in cancer therapy. These therapies are unique, as the primary target is not the tumor cell itself, but the crosstalk between immune cells and cancer cells in the tumor microenvironment. We described a negative prognostic impact of PD-L1 expression on tumor cells in esophago-gastric adenocarcinoma (GC) and CKI is effective in metastatic disease. Interestingly, efficacy of CKI is often not limited to patients with expression of the relevant protein on tumor cells. Recent publications demonstrate that expression of PD-L1 on tumor-infiltrating lymphocytes and tumor cells are of similar importance for immune escape, which explains treatment response in patients with PD-L1 negative tumors. Despite the promising results of early studies, only a minor fraction of patients responds to CKI. Preexisting endogenous immune responses seem to be crucial for immune checkpoint inhibition. A successful immune recognition depends on a broad spectrum of immune-related tumor cell intrinsic or extrinsic aspects and can so far only be predicted partially by very few markers (e.g. mutational burden, PD-L1 expression). Hence, multidimensional analyses of tumor immunogenicity including the immune infiltrate, private and shared tumor antigens, tumor specific immune response and immune escape are crucial to further improve therapeutic efficacy and translational research for this novel aspect of cancer therapy.
We aim to decipher endogenous tumor-specific immune response with a clear focus on GI Cancer. Detailed analyses of endogenous immune response against private and shared antigens will be performed using genomic and functional analyses in preclinical models, untreated tumor samples and patients receiving immune checkpoint inhibition.

Clinical/medical relevance and sustainability in disease understanding

Our research has immediate translational relevance as endogenous immune response is probably the most relevant factor determining success or failure of emerging immunotherapies. Taken together, our analyses hopefully contribute to an implementation of immunotherapy into treatment algorithms of gastrointestinal cancer, improve translational analyses and support a tailored design of future clinical trials. This could be of similar relevance to cancers of different origins.

  • Kramer M, Plum PS, Velazquez Camacho O, Folz-Donahue K, Thelen M, Garcia-Marquez I, Wolwer C, Busker S, Wittig J, Franitza M, Altmuller J, Loser H, Schlosser H, Buttner R, Schroder W, Bruns CJ, Alakus H, Quaas A, Chon SH, and Hillmer AM (2020). Cell type-specific transcriptomics of esophageal adenocarcinoma as a scalable alternative for single cell transcriptomics. Mol Oncol 14, 1170-84.
     
  • Leuchte K, Staib E, Thelen M, Godel P, Lechner A, Zentis P, Garcia-Marquez M, Waldschmidt D, Datta RR, Wahba R, Wybranski C, Zander T, Quaas A, Drebber U, Stippel DL, Bruns C, von Bergwelt-Baildon M, Wennhold K, and Schlosser HA (2020). Microwave ablation enhances tumor-specific immune response in patients with hepatocellular carcinoma. Cancer Immunol Immunother 10.1007/s00262-020-02734-1.
     
  • Oberbeck S, Schrader A, Warner K, Jungherz D, Crispatzu G, von Jan J, Chmielewski M, Ianevski A, Diebner HH, Mayer P, Kondo Ados A, Wahnschaffe L, Braun T, Muller TA, Wagle P, Bouska A, Neumann T, Putzer S, Varghese L, Pflug N, Thelen M, Makalowski J, Riet N, Gox HJM, Rappl G, Altmuller J, Kotrova M, Persigehl T, Hopfinger G, Hansmann ML, Schlosser H, Stilgenbauer S, Durig J, Mougiakakos D, von Bergwelt-Baildon M, Roeder I, Hartmann S, Hallek M, Moriggl RH, Bruggemann M, Aittokallio T, Iqbal J, Newrzela S, Abken H, and Herling M (2020). Non-canonical effector functions of the T-memory-like T-PLL cell are shaped by cooperative TCL1A and TCR signaling. Blood 10.1182/blood.2019003348.
     
  • Renner AM, Ilyas S, Schlosser HA, Szymura A, Roitsch S, Wennhold K, and Mathur S (2020). Receptor-Mediated In Vivo Targeting of Breast Cancer Cells with 17alpha-Ethynylestradiol-Conjugated Silica-Coated Gold Nanoparticles. Langmuir : the ACS journal of surfaces and colloids 10.1021/acs.langmuir.0c02820.
     
  • Wagener-Ryczek S, Schoemmel M, Kraemer M, Bruns C, Schroeder W, Zander T, Gebauer F, Alakus H, Merkelbach-Bruse S, Buettner R, Loeser H, Thelen M, Schlosser HA, and Quaas A (2020). Immune profile and immunosurveillance in treatment-naive and neoadjuvantly treated esophageal adenocarcinoma. Cancer Immunol Immunother 69, 523-33.
     
  • Zhao Y, Li J, Li D, Wang Z, Zhao J, Wu X, Sun Q, Lin PP, Plum P, Damanakis A, Gebauer F, Zhou M, Zhang Z, Schlosser H, Jauch KW, Nelson PJ, and Bruns CJ (2020). Tumor biology and multidisciplinary strategies of oligometastasis in gastrointestinal cancers. Semin Cancer Biol 60, 334-43.
     
  • Zhou C, Fan N, Liu F, Fang N, Plum PS, Thieme R, Gockel I, Gromnitza S, Hillmer AM, Chon SH, Schlosser HA, Bruns CJ, and Zhao Y (2020). Linking Cancer Stem Cell Plasticity to Therapeutic Resistance-Mechanism and Novel Therapeutic Strategies in Esophageal Cancer. Cells 9.
Dr. Hans A Schlößer CMMC Cologne
Dr. Hans A Schlößer

Clinic of General, Visceral, Tumor and Transplantation Surgery / RG location - CMMC Building

Principal Investigator CAP 12

+49 221 478 89612

+49 221 478 4833

Clinic of General, Visceral, Tumor and Transplantation Surgery / RG location - CMMC Building

Robert-Koch-Str. 21

50931 Köln

CMMC Profile Page

Curriculum Vitae (CV)

Publications - Hans A Schlößer

Link to PubMed

Group Members

Kerstin Wennhold (PostDoc)
Maria Garcia-Marquez
(PostDoc)
Martin Thelen
(PhD student)
Elena Staib
(MD Student)
Alexandra Kryscio
(Master student)
Rabi Raj Datta
(MD, clinical associate)
Philipp Gödel
(MD, clinical associate)
Sibylle Mellinghoff
(MD, clinical associate)
Katharina Leuchte
(MD, clinical associate)
Isabel Garcia-Marquez
(Technician)
Pauline Volkmar
(Technician)
Sabrina Reuter
(Technician)