Sharma et al. identified the commensal LPIMB19 (LP) as a stimulator of CD8+ T cell responses, and verified its efficacy in multiple solid tumor models, including a human BLCA organoid model. The primary immunogenic effector was the capsular polysaccharide RHP, which endowed TILs with an effector-like cytotoxic phenotype and induced macrophage activation dependent on TLR2. Iron transport was upregulated in i.t. macrophages, promoting iron uptake (via LCN2 secretion), with concomitant depletion of iron in tumor cells and enhanced apoptosis. Both TLR2 and LCN2 were required for antitumor efficacy, suggesting a role for macrophage-mediated “nutritional immunity”.
Contributed by Morgan Janes
ABSTRACT: Innate immune cells generate a multifaceted antitumor immune response, including the conservation of essential nutrients such as iron. These cells can be modulated by commensal bacteria; however, identifying and understanding how this occurs is a challenge. Here we show that the food commensal Lactiplantibacillus_plantarum IMB19 augments antitumor immunity in syngeneic and xenograft mouse tumor models. Its capsular heteropolysaccharide is the major effector molecule, functioning as a ligand for TLR2. In a two-pronged manner, it skews tumor-associated macrophages to a classically active phenotype, leading to generation of a sustained CD8(+) T cell response, and triggers macrophage 'nutritional immunity' to deploy the high-affinity iron transporter lipocalin-2 for capturing and sequestering iron in the tumor microenvironment. This process induces a cycle of tumor cell death, epitope expansion and subsequent tumor clearance. Together these data indicate that food commensals might be identified and developed into 'oncobiotics' for a multi-layered approach to cancer therapy.
Author Info: (1) Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, Republic of Korea. ImmunoBiome, Bio Open Innovation Center, Pohang, Republic of Kore
Author Info: (1) Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, Republic of Korea. ImmunoBiome, Bio Open Innovation Center, Pohang, Republic of Korea. (2) Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, Republic of Korea. Innovation Research Center for Bio-future Technology (B-IRC), Pohang University of Science and Technology (POSTECH), Pohang, Republic of Korea. (3) ImmunoBiome, Bio Open Innovation Center, Pohang, Republic of Korea. (4) Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, Republic of Korea. Department of New Biology, Daegu Gyeongbuk Institute of Science and Technology (DGIST), Daegu, Republic of Korea. (5) Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, Republic of Korea. (6) Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, Republic of Korea. Department of New Biology, Daegu Gyeongbuk Institute of Science and Technology (DGIST), Daegu, Republic of Korea. (7) Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, Republic of Korea. (8) Institute of Molecular Biology and Genetics, Seoul National University, Seoul, Republic of Korea. (9) Department of Urology, College of Medicine, Seoul National University Hospital, Seoul, Republic of Korea. (10) Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, Republic of Korea. Department of New Biology, Daegu Gyeongbuk Institute of Science and Technology (DGIST), Daegu, Republic of Korea. (11) Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, Republic of Korea. (12) Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, Republic of Korea. (13) Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, Republic of Korea. (14) ImmunoBiome, Bio Open Innovation Center, Pohang, Republic of Korea. (15) Department of Chemical Sciences, University of Napoli Federico II Complesso Universitario Monte Santangelo, Via Cintia 4, I-80126, Naples, Italy. (16) Clinical Vaccine R&D Center and Combinatorial Tumor Immunotherapy MRC, Chonnam National University, Hwasun-gun, Republic of Korea. (17) Clinical Vaccine R&D Center and Combinatorial Tumor Immunotherapy MRC, Chonnam National University, Hwasun-gun, Republic of Korea. (18) College of Pharmacy and Integrated Research Institute for Drug Development, Dongguk University, Seoul, Republic of Korea. (19) Department of Chemical Sciences, University of Napoli Federico II Complesso Universitario Monte Santangelo, Via Cintia 4, I-80126, Naples, Italy. (20) Department of Chemical Sciences, University of Napoli Federico II Complesso Universitario Monte Santangelo, Via Cintia 4, I-80126, Naples, Italy. (21) Institute of Molecular Biology and Genetics, Seoul National University, Seoul, Republic of Korea. Department of Biological Sciences, College of Natural Sciences, Seoul National University, Seoul, Republic of Korea. (22) Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, Republic of Korea. (23) Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, Republic of Korea. Department of New Biology, Daegu Gyeongbuk Institute of Science and Technology (DGIST), Daegu, Republic of Korea. (24) ImmunoBiome, Bio Open Innovation Center, Pohang, Republic of Korea. drudra@shanghaitech.edu.cn. School of Life Science and Technology, ShanghaiTech University, Shanghai, China. drudra@shanghaitech.edu.cn. (25) Department of Life Sciences, Pohang University of Science and Technology (POSTECH), Pohang, Republic of Korea. iimsh@postech.ac.kr. ImmunoBiome, Bio Open Innovation Center, Pohang, Republic of Korea. iimsh@postech.ac.kr. Institute for Convergence Research and Education in Advanced Technology, Yonsei University, Seoul, Republic of Korea. iimsh@postech.ac.kr.
