We report that intratumoral Tertiary Lymphoid Structures (TLS) in human ovarian cancer contain highly oligoclonal B cells that produce IgA and IgG. Using a recombinant antibody cloned from the dominant sequence of an ovarian cancer TLS, we abrogated the growth of the autologous human tumor in vivo, through recognition of the extracellular domain of tumor-promoting GPR85. TLS-derived antibodies therefore contribute to anti-tumor immunity, which could be leveraged for novel immunotherapies.