Cytotoxic function of gamma delta (gamma/delta) T cells against pamidronate-treated cervical cancer cells.
The cytotoxic function of polyclonal expanded gamma/delta T cells against pamidronate-treated cervical cancer cells in vitro and in vivo were determined. The gamma/delta T cells were isolated and purified from PBMCs by using miniMACS and were later treated with 10 microM pamidronate. The expansion of gamma/delta T cells was 15 times more than the non-stimulated cells. Among the expanded gamma/delta T cells, 47% were Vgamma9/Vdelta2 T cells with a purity of 87%. Analyzing the cytotoxic function of gamma/delta T cells against 3 cervical cancer cells in vitro by LDH cytotoxicity test revealed that the killing efficacy increased if the cervical cancer cells (HeLa, SiHa and CaSki) were pretreated with pamidronate. The presence of CD107 on gamma/delta T cells indicated the degranulation of perforin and granzyme pathway is one of the mechanisms used by the gamma/delta T cells to kill cancer cells. The killing ability of gamma/delta T cells against cancer cells in vivo was preliminary assessed by using mouse baring HeLa cells. The results demonstrated that gamma/delta T cells induce apoptosis in tumor cells. Our study supports the usefulness of gamma/delta T cells in future development of immunotherapy for cervical cancer.
Interdisciplinary Program of Medical Microbiology, Graduate School, Chulalongkorn University, Bangkok 10330, Thailand.
Monthon
M
Lertworapreecha
Suthiluk
S
Patumraj
Somchai
S
Niruthisard
Pokrath
P
Hansasuta
Parvapan
P
Bhattarakosol
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D016207:Cytokines / Q000378:metabolism; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D004164:Diphosphonates / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D000077268:Pamidronate; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D014407:Tumor Cells, Cultured; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology*
D000970:Antineoplastic Agents; D016207:Cytokines; D004164:Diphosphonates; D016692:Receptors, Antigen, T-Cell, gamma-delta; D000077268:Pamidronate