Protein-calorie malnutrition inhibits antitumor response to interleukin-2 immunotherapy.
The efficacy of systemic interleukin-2 (IL-2) immunotherapy is dependent on a competent host immune response. This study demonstrated that protein-calorie malnutrition (PCM) inhibited the generation of an antitumor response to IL-2. A/J mice received an isocaloric diet of 2.5% or 24% casein 8 weeks before inoculation with C1300 neuroblastoma cells. Three weeks later lymphocytes from tumor-bearing mice were harvested for determination of cytotoxic T-lymphocyte generation and natural killer cell cytotoxicity. PCM produced a significant reduction in total body weight (p less than 0.001) and serum albumin concentration (p less than 0.001). PCM inhibited generation of cytotoxic T lymphocytes (p less than 0.001), T-lymphocyte response in mixed lymphocyte reaction (p less than 0.001), and in vitro activation of natural killer cell cytotoxicity with IL-2 (p less than 0.001). A second experiment was performed to evaluate whether the in vitro deficits in tumor-specific and natural immunity in the animal model of PCM would diminish the efficacy of systemic high-dose IL-2 (3 x 10(6) units/kg three times daily for 5 days). The mean percent inhibition of C1300 growth with IL-2 was only 15% in mice with PCM compared with 60% in well-nourished mice (p less than 0.01). Median host survival time was greater in well-nourished animals (55 days) compared with animals with PCM (39 days) that received IL-2 (p less than 0.05). These data suggest that nutritional status is a critically important variable in tumoricidal response to systemic IL-2.
Lieberman
M D
MD
Division of Surgical Oncology, University of Pennsylvania School of Medicine, Philadelphia.
Reynolds
J
J
Goldfine
J
J
Shou
J
J
Daly
J M
JM
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001696:Biomechanical Phenomena; D001835:Body Weight; D007167:Immunotherapy; D007376:Interleukin-2 / Q000627:therapeutic use*; D007519:Isoantigens / Q000276:immunology; D051379:Mice; D008815:Mice, Inbred Strains; D011502:Protein-Energy Malnutrition / Q000097:blood / Q000473:pathology / Q000503:physiopathology*; D012709:Serum Albumin / Q000032:analysis; D013602:T-Lymphocytes, Cytotoxic / Q000502:physiology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
D000970:Antineoplastic Agents; D007376:Interleukin-2; D007519:Isoantigens; D012709:Serum Albumin