The present invention relates to compositions and methods for immunotherapy of a subject afflicted with diseases such as cancer, an infectious disease, or a neurodegenerative disease, which methods comprise administering to the subject a composition comprising a therapeutically effective amount of an anti-PD-L1 antibody or portion thereof that potentiates an endogenous immune response, either stimulating the activation of the endogenous response or inhibiting the suppression of the endogenous response.