We are currently interested in analyzing the non-peptidic ligands recognized by γδ T cells on tumor cells. Our studies demonstrate that T lymphocytes expressing the Vγ9/Vδ2 TCR recognize non-peptidic phosphorylated compounds, their synthetic analogs bisphosphonates and endogenous metabolite Isopentenyl pyrophosphate (intermediate metabolite of mevalonate pathway) in tumor cells. γδ T cells release IFN-gamma and TNF-alpha after co-culture with a panel of oral, breast and prostate tumor cell lines as against lowered cytokines in normal, non-transformed cell lines. Chromium release assay and flow cytometry data reveal increased cytotoxicity of γδ T cells upon activation with bisphosphonates. Current studies aim to identify the nexus between γδ T cells and osteoclasts/ osteoblasts vis-à-vis their role in bone metabolism.