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Principal Investigator: Irina Matei
Organization: WEILL MEDICAL COLL OF CORNELL UNIV
Fiscal Year: 2024
Award: $188,198
Funding agency: National Cancer Institute
ABSTRACT
Cancer progression and metastasis account for the majority of cancer- related deaths, yet how
cancer overcomes the immune system to metastasize is only beginning to be understood. The
promise of immunotherapies has underscored how integral the host immune cells are in
controlling cancer progression and the critical role of the gut microbiome in modulating responses
to immunotherapies. However, we have yet to determine how gut microbiome-immune system
interactions modulate cancer metastasis, identify gut microbes associated with metastatic risk,
or shift immunotherapy paradigms to proactively attack potential metastases.
Recent studies highlighted the role of B cells in immune regulation of tumor progression, as tumor-
infiltrating B cells positively associated with improved responses to immunotherapies and
favorable prognosis. However, the co-existence of both anti- and pro-tumorigenic B cell
populations during cancer progression complicates the approach to studying the functions of
tumor-infiltrating B cells. Since immunoglobulin G (IgG) antibodies mediate clearance of
pathogens and tumor cells with high affinity and specificity and we recently showed that IgG
antibodies target specific gut bacteria, modulating the gut microbiome at steady state, we propose
a focused approach to dissect the role of humoral immunity in anti-tumor responses during tumor
progression. We hypothesize that the interplay between IgG and gut microbiome will be critical in
hindering well defined, sequential steps during tumor progression by shaping the tumor immune
microenviroment as well as systemic anti-tumor responses. Thus, we will use a novel model of
immunoglobulin G (IgG) deficiency developed by Dr. Zeng to dissect the specific role of IgG
production in hindering tumor progression, independent of that of other B cell functions, and to
investigate how IgG response to the tumor modulates the gut microbiome and thereby affecting
anti-tumor immunity. The role of immunoglobulin G in tumor progression has not yet been
systematically evaluated, especially during the pre-metastatic, micro-metastatic or macro-
metastatic stages of tumor metastasis. Moreover, the interplay between the gut microbiome and
B cell subsets, the development of anti-tumor humoral immunity and memory B cell repertoires
remain unexplored. We propose that combining the novel animal model lacking IgG with well
characterized tumor models and comprehensive phenotypic and functional characterization of
relevant immune subsets will allow this interdisciplinary team to dissect the role of antibodies in
cancer progression and determine how the interplay between the gut microbiome and IgG shapes
anti-tumor immunity and cancer progression.
Terms: <7S Gamma Globulin><Acceleration><Affect><Affinity><Animal Model><Animal Models and Related Studies><Antibodies><Antitumor Response><B blood cells><B cell><B cell repertoire><B cells><B-Cell Subsets><B-Cells><B-Lymphocyte Subsets><B-Lymphocytes><B-cell><CSIF><CSIF-10><Cancer Control><Cancer Control Science><Cancer Model><Cancer Treatment><CancerModel><Cancers><Cell Body><Cell Communication><Cell Function><Cell Interaction><Cell Physiology><Cell Process><Cell-to-Cell Interaction><Cells><Cellular Function><Cellular Physiology><Cellular Process><Cessation of life><Compensation><Cross Presentation><Cytokine Synthesis Inhibitory Factor><Data><Death><Development><Disease><Disorder><Elderly><Enhancers><GI microbiome><Germ-Free><Humoral Immunities><IL-10><IL10><IL10A><IgG><Immune><Immune Globulins><Immune Markers><Immune Surveillance><Immune mediated therapy><Immune response><Immune system><Immunes><Immunoglobulin G><Immunoglobulins><Immunologic Markers><Immunologic Surveillance><Immunologic Surveillances><Immunological Surveillance><Immunological Surveillances><Immunological response><Immunologically Directed Therapy><Immunologist><Immunology><Immunomodulation><Immunosurveillance><Immunotherapy><Impairment><Infiltration><Inflammation><Interleukin 10 Precursor><Interleukin-10><Investigation><KO mice><Knock-out Mice><Knockout Mice><Lead><MICMET><Malignant Melanoma><Malignant Neoplasm Therapy><Malignant Neoplasm Treatment><Malignant Neoplasms><Malignant Ovarian Neoplasm><Malignant Ovarian Tumor><Malignant Soft Tissue Neoplasm><Malignant Tumor><Malignant Tumor of the Ovary><Malignant neoplasm of ovary><Mediating><Melanoma><Memory B Cell><Memory B-Lymphocyte><Metastasis><Metastasize><Metastatic Lesion><Metastatic Mass><Metastatic Neoplasm><Metastatic Tumor><Mice><Mice Mammals><Microbe><Micrometastasis><Micromets><Modeling><Molecular Tumor Suppression><Murine><Mus><Myeloid-derived suppressor cells><Neoplasm Metastasis><Null Mouse><Ovary Cancer><Pathway interactions><Patients><Pb element><Phenotype><Play><Population><Predisposition><Primary Neoplasm><Primary Tumor><Principal Investigator><Production><Prognosis><Risk><Role><Sarcoma><Science><Secondary Neoplasm><Secondary Tumor><Shapes><Specificity><Subcellular Process><Susceptibility><T-Stage><Therapeutic><Transplantation><Treatment outcome><Tumor Antigens><Tumor Cell><Tumor Immunity><Tumor Promotion><Tumor Suppression><Tumor stage><Tumor-Associated Antigen><adaptive immune response><advanced age><animal facility><anti-cancer immunotherapy><anti-cancer therapy><anti-tumor immune response><anti-tumor immunity><anti-tumor response><antibody-based immunity><anticancer immunotherapy><antitumor immunity><bacteria in the gut><cancer antigens><cancer biomarkers><cancer immunity><cancer immunotherapy><cancer markers><cancer metastasis><cancer microenvironment><cancer progression><cancer therapy><cancer-directed therapy><cytotoxic CD8 T cells><cytotoxic CD8 T lymphocyte><developmental><digestive tract microbiome><enteric microbiome><fighting><fitness><gastrointestinal microbiome><geriatric><gut bacteria><gut microbes><gut microbial species><gut microbiome><gut-associated microbiome><heavy metal Pb><heavy metal lead><host response><immune microenvironment><immune modulation><immune regulation><immune system response><immune therapeutic approach><immune therapeutic interventions><immune therapeutic regimens><immune therapeutic strategy><immune therapy><immune-based biomarkers><immune-based cancer therapies><immune-based therapies><immune-based treatments><immuno therapy><immunologic reactivity control><immunological biomarkers><immunological markers><immunomodulatory><immunoregulation><immunoregulatory><immunoresponse><immunosuppressive microenvironment><immunosuppressive myeloid cells><immunosuppressive tumor microenvironment><immunotherapy for cancer><immunotherapy of cancer><improved><intestinal biome><intestinal microbes><intestinal microbiome><malignancy><malignant soft tissue tumor><microbial><microbial products><model of animal><mouse model><multidisciplinary><murine model><myeloid suppressor cells><myeloid-derived suppressive cells><neoplasm progression><neoplasm/cancer><neoplastic cell><neoplastic progression><novel><ovarian cancer><pathogen><pathway><prevent><preventing><recruit><response><senior citizen><social role><suppressive myeloid cells><transplant><tumor><tumor cell metastasis><tumor growth><tumor immune microenvironment><tumor microenvironment><tumor progression><tumor-immune system interactions><tumor-specific antigen><tumorigenic><uptake>