Lieberman M D, Reynolds J, Redmond H P, Leon P, Shou J, Daly J M
Division of Surgical Oncology, University of Pennsylvania School of Medicine, Philadelphia.
JPEN J Parenter Enteral Nutr. 1991 Jan-Feb;15(1):15-21. doi: 10.1177/014860719101500115.
Protein-calorie malnutrition (PCM) is prevalent in cancer patients. However, the effect of PCM on anti-tumor immunity is unclear and critically important in an era of improving results with adoptive immunotherapy. This study examined the effect of short- and long-term PCM on tumor-specific and natural immune effector mechanisms in a murine neuroblastoma (C1300 NRB) model. A/J mice received an isocaloric 2.5% or 24% casein diet for 3 or 8 weeks before inoculation with tumor. Three weeks later lymphocytes from tumor-bearing mice were harvested for determination of cytotoxic T lymphocyte (CTL) generation and natural killer (NK) cell cytotoxicity. Both 3 and 8 weeks of PCM significantly reduced mean total body weight by 25% (p less than 0.001) and 41% (p less than 0.001), respectively, compared with regularly nourished mice. Short-term PCM did not inhibit CTL or NK cytotoxicity, whereas long-term PCM significantly diminished CTL generation (p less than 0.001) but preserved NK cytotoxic function. These results indicate that CTL development against autologous tumor, in contrast to basal NK function, is dependent on host nutritional status. Mean tumor growth, determined by tumor-weight to carcass-weight ratio, was unchanged for both short- and long-term protein-energy deprived groups compared with results in regularly nourished mice. These findings suggest that NK function is the predominant effector mechanism inhibiting C1300 NRB growth and that NK tumoricidal capacity is preserved during PCM.
蛋白质 - 热量营养不良（PCM）在癌症患者中普遍存在。然而，在过继性免疫治疗效果不断改善的时代，PCM对抗肿瘤免疫的影响尚不清楚且至关重要。本研究在小鼠神经母细胞瘤（C1300 NRB）模型中，检测了短期和长期PCM对肿瘤特异性和天然免疫效应机制的影响。A/J小鼠在接种肿瘤前3周或8周接受等热量的2.5%或24%酪蛋白饮食。3周后，收集荷瘤小鼠的淋巴细胞，用于测定细胞毒性T淋巴细胞（CTL）生成和自然杀伤（NK）细胞的细胞毒性。与正常营养的小鼠相比，3周和8周的PCM分别使平均总体重显著降低了25%（p<0.001）和41%（p<0.001）。短期PCM未抑制CTL或NK细胞毒性，而长期PCM显著减少了CTL生成（p<0.001），但保留了NK细胞毒性功能。这些结果表明，与基础NK功能相比，针对自体肿瘤的CTL发育依赖于宿主营养状况。通过肿瘤重量与胴体重量比确定的平均肿瘤生长，短期和长期蛋白质 - 能量剥夺组与正常营养小鼠的结果相比均未改变。这些发现表明，NK功能是抑制C1300 NRB生长的主要效应机制，且在PCM期间NK的杀瘤能力得以保留。
