The spleen plays an immunosuppressive role in patients with gastric cancer: involvement of CD62L+ cells and TGF-beta.
CD62L is the human homologue of the murine lymphocyte homing receptor, mel-14. We investigated CD62L + cells in the spleen from patients with gastric cancer. Flow cytometric analysis revealed that CD62L + cells were decreased in the peripheral blood, but inversely increased in the spleen in parallel with disease progression in gastric cancer patients. The increased CD62L+ cells resided in the CD4+ suppressor-inducer phenotype, and the removal of CD62L+ cells from spleen cells resulted in a decrease of concanavalin-A-induced suppressor activity in vitro in one-way allogeneic mixed lymphocyte reaction. The CD62L+ cells included CD4+CD25+ regulatory T cells. The culture supernatant of CD62L + cells showed TGF-beta activity that permitted anchorage-independent growth of normal rat kidney (NRK) cells in a soft agar. TGF-beta activity was more significantly detectable in the splenic vein than in the peripheral blood, and TGF-beta mRNA was detectable in the spleen from advanced gastric cancer patients. These results suggest that CD62L+ cells migrate into the spleen with disease progression of gastric cancer and serve as suppressor-inducer cells with TGF-beta production to induce regulatory T cells, contributing to disease-associated immunosuppression in advanced gastric cancer patients.
Noma
Kosuke
K
Department of Surgical Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Minami-Ku, Hiroshima 734-8553, Japan.
Yamaguchi
Yoshiyuki
Y
Okita
Riki
R
Matsuura
Kazuo
K
Toge
Tetsuya
T
D000368:Aged; D001681:Biological Assay; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D002465:Cell Movement; D003208:Concanavalin A / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D019041:L-Selectin / Q000096:biosynthesis*; D008214:Lymphocytes / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000166:cytology / Q000276:immunology* / Q000502:physiology*; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000096:biosynthesis* / Q000378:metabolism
D007166:Immunosuppressive Agents; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2; D016212:Transforming Growth Factor beta; D003208:Concanavalin A; D019041:L-Selectin