Immune Regulation in Cancer and Stem Cell Transplantation

Arbeitsgruppe PD Dr. med. Poeck

Research Interests

Regenerative responses after allogeneic hematopoietic stem cell transplantation (allo-HSCT):

Our data suggest that endogenous cytosolic nucleic acid receptors including RIG-I-MAVS and cGAS-STING are involved in protecting epithelial integrity during GVHD and that therapeutic activation of RIG-I/MAVS can be exploited therapeutically to maintain epithelial barrier integrity and prevent GVHD. Our goal is to characterize the role of intestinal microbiota (bacterial / fungal) on the ISC compartment and immune system after damage induced by allo-HSCT and at understanding the innate immune pathways that can regulate barrier function after inflammatory tissue damage. We hypothesize that (i) endogenous bacteria and fungi will modulate the production of factors that are critical for intestinal homeostasis and self-renewal, and possibly support tissue regeneration by directly or indirectly activating of Lgr5+ ISC and/or its niche (Paneth cells) from intestinal pathology during pre-transplant conditioning or GVHD and (ii) microbiota (bacterial and/or fungal)-mediated tissue regeneration during GVHD is regulated by the indicated innate immune pathways. Our goal is to find ways to manipulate stem cell dynamics in order to improve prevention methods and therapies. Please find below a schematic overview of my current research projects related to ISCs:

Schematic overview of the projects related to allogeneic hematopoietic stem cell transplantation (allo-HSCT):
Conditioning therapy-mediated damage to intestinal stem cells (ISCs) and other intestinal epithelial cells (IEC) leads to barrier function loss and translocation of otherwise luminal gut microbiota and release of danger-associated molecular patterns (DAMPs) (A). This triggers activation of recipient antigen presenting cells (APCs) that resisted the conditioning regime (B). Strong stimulation of recipient APCs results in enhanced cytokine production(B), priming and expansion of transplanted allogeneic donor T cells (C). Following an expansion phase, donor T cells can home to particular organs (gut, liver, skin) where destruction of allogeneic tissue of the recipient ultimately causes morbidity and mortality of GVHD. Thus, strategies to enhance ISC-mediated tissue regeneration are crucial for maintaining epithelial intestinal barrier function for the prevention of Graft versus host disease (GVHD) following conditioning therapy and allogeneic hematopoietic stem cell transplantation (allo-HSCT).


Mechanisms of immune evasion and activation in tumor cells and their tumor microenvironment:

Our data identify tumor-intrinsic RIG-I signaling as a fundamental requirement for natural and therapy-mediated (immune checkpoint blockade (ICB)) antitumor immunity. Yet, malignant melanomas can evade IFN-I-dependent immune surveillance, implicating immuno-inhibitory mechanisms that may contribute to immune escape of melanoma and render these innate pathways insensitive to activation. Our goal is to define the contributions of aberrant (defective) tumor-intrinsic and host-dependent innate immune pathways during development and immunosurveillance of melanoma and other cancers as well as to identify the mechanisms and environmental factors (microbiome, metabolites, extracellular vesicles) that drive disease resistance and response to established immunotherapy protocols (i.e. ICB, radiation therapy, demethylating agents). We anticipate that our results will yield significant insights into improving outcomes of cancer patients as well as reveal molecular processes that are fundamental to immune –cancer cell communication. Please find below a schematic overview of my current research projects related to cancer resistance and immunotherapy:

Schematic overview of the current projects related to cancer immunotherapy:
Genotoxic therapies and therapeutic nucleic acids can trigger potent IFN responses in antigen-presenting cells and simultaneously elicit immunogenic forms of cell death in cancer cells. Both mechanisms can lead to potent anti-tumor responses. Yet, cancers can also evade IFN-I-dependent immune surveillance, implicating immuno-inhibitory mechanisms that may contribute to immune escape of cancer and render these innate pathways insensitive to activation. Thus, better insights into the mechanisms that drive disease resistance and response to established immunotherapy protocols are urgently needed.

Application

Written applications including CV are welcome and should be forwarded by e-mail(link sends e-mail) to Dr. med. Hendrik Poeck

 

Third party funding

EMBO (Young Investigator Programme)
European Hematology Association (EHA)
DKMS Foundation for Giving Life (DKMS)
SFB 1335 (German research foundation (DFG))
SFB 1371 (German research foundation (DFG))
Else-Kröner Fresenius-Stiftung (EKFS)
Promotionsprogramm „Translationale Medizin“ of the TU München

 

Ihr Ansprechpartner

   

PD Dr. med.
Hendrik Poeck
Principal Investigator

Laboratory: TranslaTUM

E-Mail(link sends e-mail)