Tumor-draining lymph nodes of primary lung cancer patients: a potent source of tumor-specific killer cells and dendritic cells.
BACKGROUND
The tumor-draining lymph node tissue (TDLT) of lung cancer patients generated killer cells specific to autologous tumor cells when cultured with low dose IL-2. This production of killer cells lasted as long as 2 months after the initiation of the culture (productive phase). Even after this productive phase, TDLT supported the generation of the killer cells when these were co-cultured with peripheral blood lymphocytes (PBL) from the same patients. We tried to analyze the mechanisms of this production of killer cells from TDLT.


METHODS
TDLT, tumor tissues as well as PBL were obtained from primary lung cancer patients and cultured in vitro. Cell growth, cell surface markers and specific cytotoxic activity of the lymphocytes were examined.


RESULTS
The majority of the cells from TDLT or TDLT+ PBL co-culture (TDL-Pb) were CD3-positive T cells (89-99%) and a 51Cr-releasing assay showed that these cells had a stronger cytotoxic activity against autologous tumor cells than cells from PBL cultured with IL-2. Their activity against allogeneic MHC incompatible target cells was not, however, elevated. Cytotoxic activity against autologous tumor cells was blocked by anti-HLA class 1 (52.0%), class 11 (47.9%) and CD8 (46.8%) antibodies, but not by anti-CD56 antibody. The treatment of TDLT with anti-CD8, CD4, CD80 and CD83 all together completely abrogated the ability of TDLT to generate killer cells, with one of these antibodies it did so partially, while treatment with anti-CD56 antibody failed to do so at all.


CONCLUSIONS
These results collectively suggest that TDLT contains tumor antigen-pulsed DCs as well as precursors of specific killer T cells and gives rise to the generation of killer cells when cultured in a low dose of IL-2.
Kimura
Hideki
H
Chiba Cancer Center, Nitona-cho 666-2, Chuo-ku, Chiba City, Chiba 260-8717, Japan. lung@chiba-cc.jp
Dobrenkov
Konstantin
K
Iida
Tomohiko
T
Suzuki
Makoto
M
Ando
Sohichiro
S
Yamamoto
Naotaka
N
D000230:Adenocarcinoma / Q000097:blood / Q000276:immunology / Q000473:pathology; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D002294:Carcinoma, Squamous Cell / Q000097:blood / Q000276:immunology / Q000473:pathology; D018920:Coculture Techniques; D003602:Cytotoxicity, Immunologic / Q000187:drug effects / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology* / Q000473:pathology; D005260:Female; D015234:HLA-A Antigens / Q000276:immunology; D015235:HLA-B Antigens / Q000276:immunology; D006684:HLA-DR Antigens / Q000276:immunology; D006801:Humans; D007376:Interleukin-2 / Q000276:immunology / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology*; D008175:Lung Neoplasms / Q000097:blood / Q000276:immunology* / Q000473:pathology; D008198:Lymph Nodes / Q000276:immunology* / Q000473:pathology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology; D008297:Male; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology
D000911:Antibodies, Monoclonal; D015234:HLA-A Antigens; D015235:HLA-B Antigens; D006684:HLA-DR Antigens; D007376:Interleukin-2