Talks
Targeting tumor associated macrophages to improve the immunotherapy of pancreatic cancer
Presentation Type
Oral Presentation
Discipline Track
Clinical Science
Abstract Type
Research/Clinical
Abstract
Background: Tumor associated macrophages (TAMs) represent a major component of immune infiltrating leukocytes in tumor microenvironment. Soluble factors secreted by TAMs have been shown to promote cancer progression by establishing an immunosuppressive microenvironment that inhibits antitumor T-cell responses. TAMs also mediate resistance to conventional chemotherapies and contemporary targeted regimens. Therefore, targeting TAMs could be a novel approach to improve tumor immune surveillance and maximize the current chemo/immunotherapy response.
Methods and Results: We have identified that a probiotic strain (Lactobacillus casei) derived siderophore (ferrichrome) efficiently reprograms Tumor-Associated Macrophages (TAMs) and increases CD8+ T cell infiltration into tumors that paralleled a marked reduction in tumor burden in a syngeneic mouse model of pancreatic cancer. Interestingly, this altered immune response improved anti-PD-L1 therapy that suggests promise of a novel combination (ferrichrome and immune checkpoint inhibitors) therapy for pancreatic cancer treatment. Mechanistically, ferrichrome induced TAMs polarization via activation of the TLR4 pathway that represses the expression of iron export protein ferroportin (FPN1) in macrophages.
Conclusion: This study describes a novel probiotic based molecular mechanism that can effectively induce anti-tumor immunosurveillance and improve checkpoint blockade immunotherapy response against pancreatic cancer.
Academic/Professional Position
Faculty
Academic/Professional Position (Other)
PhD
Mentor/PI Department
Immunology and Microbiology
Recommended Citation
Chaib, Mehdi; Yallapu, Murali M.; Jaggi, Meena; Chauhan, Subhash C.; and Hafeez, Bilal B., "Targeting tumor associated macrophages to improve the immunotherapy of pancreatic cancer" (2023). Research Symposium. 60.
https://scholarworks.utrgv.edu/somrs/theme1/track1/60
Targeting tumor associated macrophages to improve the immunotherapy of pancreatic cancer
Background: Tumor associated macrophages (TAMs) represent a major component of immune infiltrating leukocytes in tumor microenvironment. Soluble factors secreted by TAMs have been shown to promote cancer progression by establishing an immunosuppressive microenvironment that inhibits antitumor T-cell responses. TAMs also mediate resistance to conventional chemotherapies and contemporary targeted regimens. Therefore, targeting TAMs could be a novel approach to improve tumor immune surveillance and maximize the current chemo/immunotherapy response.
Methods and Results: We have identified that a probiotic strain (Lactobacillus casei) derived siderophore (ferrichrome) efficiently reprograms Tumor-Associated Macrophages (TAMs) and increases CD8+ T cell infiltration into tumors that paralleled a marked reduction in tumor burden in a syngeneic mouse model of pancreatic cancer. Interestingly, this altered immune response improved anti-PD-L1 therapy that suggests promise of a novel combination (ferrichrome and immune checkpoint inhibitors) therapy for pancreatic cancer treatment. Mechanistically, ferrichrome induced TAMs polarization via activation of the TLR4 pathway that represses the expression of iron export protein ferroportin (FPN1) in macrophages.
Conclusion: This study describes a novel probiotic based molecular mechanism that can effectively induce anti-tumor immunosurveillance and improve checkpoint blockade immunotherapy response against pancreatic cancer.