Antibody-mediated Immune Response in Cancer Patients
The function of lymphocytes in the tumor microenvironment (TME) and their potential for reactivation for tumor cell eradication by immune checkpoint blockades have been intensively studied. Positive correlations between tertiary lymphocyte structures (TLS), the presence of B cells, and germinal centers (GCs) in tumors underscore their significance in patient survival and effective immunotherapy responses across various cancer types. Furthermore, while adaptive immune responses initiate in lymphoid organs, the contribution of tumor-draining lymph nodes (TDLNs) and the role of GCs in anti-tumor immunity remain less explored. To examine B cell immune responses in cancer patients we have established collaboration with physicians from Rabin Medical Center (Beilinson Hospital) and Sheba Medical Center who provide us with tissues from ovarian cancer, head and neck squamous cell carcinoma, renal cancer and lung cancer patients. These tissues are used to address multiple questions around the problem of why the immune response is failing in cancer. In particular, we aim to investigate the functionality of GCs in TDLNs and in the (TME) and their potential to initiate an anti-tumor immune response through the antibody affinity maturation process. To address this, we utilize single-cell RNA sequencing to examine B cell subsets within TDLNs in HNSCC human patients and analyze GC B cell immunoglobulins for increased affinity and tumor binding. The functional potential of these antibodies are assessed in vitro and in vivo experiments, including tumor growth inhibition and immune cell-mediated effector functions. These studies hold the potential to uncover molecular mechanisms underlying the inability of these GCs to reject tumors and expose novel molecular mechanisms in human GCs, offering insights for clinical manipulation and therapeutic advancement. In addition, patient-derived monoclonal antibodies and their targets have the potential to be used as a new immunotherapy treatment.
