Postoperative immunosuppression cascade and immunotherapy using lymphokine-activated killer cells for patients with esophageal cancer: possible application for compensatory anti-inflammatory response syndrome.
Immunological parameters were measured in order to elucidate a postoperative immunosuppression mechanism in transthoracic esophagectomy for patients with esophageal cancer. Moreover, lymphokine-activated killer (LAK) cells were transferred just after the surgery to overcome the postoperative immunosuppression. Fifteen consecutive patients who underwent transthoracic esophagectomy were subjected to the postoperative measurement of immunological parameters. Ten patients who underwent open cholecystectomy served as controls. Heparinized venous blood was obtained pre- and postoperatively, and serum levels of cytokines IL-6 and IL-10 and immunosuppressive acidic protein (IAP) were measured. Peripheral blood lymphocytes were harvested and analyzed by flow cytometry for phenotype detection and by a mixed lymphocyte reaction for detecting concanavalin (Con)-A-induced or -non-induced suppressor activity. Another 29 consecutive patients who underwent transthoracic esophagectomy were randomly enrolled in a postoperative immunotherapy trial either with or without lymphokine-activated killer cells. It was found that, in the esophagectomy group, IL-6 and IL-10 increased postoperatively and peaked on day 1, followed by an increase in IAP, peaked again on day 4, with a profound decrease in helper and cytotoxic T-cell subsets, followed by increases in Con-A-induced (on day 7 or later) and spontaneous (on day 10) suppressor activities. These changes were minimal in the cholecystectomy group. LAK cell transfer restored the postoperative decrease in the helper and cytotoxic T-cell population, and there was a trend of reduction for postoperative remote infection such as pneumonia and surgical site infection in the LAK therapy group. Taken together, we would like to propose the existence of a postoperative immunosuppression cascade consisting of increases in cytokines and immunosuppressive proteins, decreases in helper and cytotoxic T-cell populations, and the development of suppressor T-cell activities in surgery for esophageal cancer. Postoperative adoptive transfer of LAK cells may be a novel clinical application in surgery for esophageal cancer as a means of treating this postoperative immunosuppressive condition that may be identical to the status of compensatory anti-inflammatory response syndrome (CARS).
Yamaguchi
Yoshiyuki
Y
Department of Surgical Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima 734-8553, Japan. shogo@hiroshima-u.ac.jp
Hihara
Jun
J
Hironaka
Katsuji
K
Ohshita
Akiko
A
Okita
Riki
R
Okawaki
Makoto
M
Matsuura
Kazuo
K
Nagamine
Ichiro
I
Ikeda
Takuhiro
T
Ohara
Masahiro
M
Hamai
Yoichi
Y
D000368:Aged; D002452:Cell Count; D003208:Concanavalin A / Q000494:pharmacology; D004938:Esophageal Neoplasms / Q000276:immunology / Q000601:surgery / Q000628:therapy*; D016629:Esophagectomy; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007165:Immunosuppression Therapy / Q000379:methods; D016219:Immunotherapy, Adoptive; D016753:Interleukin-10 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology* / Q000637:transplantation; D007959:Lymphocyte Culture Test, Mixed; D008214:Lymphocytes / Q000737:chemistry / Q000166:cytology / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000097:blood; D018746:Systemic Inflammatory Response Syndrome / Q000276:immunology / Q000628:therapy; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology; D013997:Time Factors
D015850:Interleukin-6; D009363:Neoplasm Proteins; C030193:immunosuppressive acidic protein; D003208:Concanavalin A; D016753:Interleukin-10