Abstract

Natural killer (NK) cell activity was measured in the peripheral blood mononuclear cells (PBMC) from malnourished (MN) and well-nourished (WN) cancer patients and in healthy controls. A marked depression of NK activity was observed in MN cancer patients with moderate protein-calorie malnutrition (PCM), but not in WN cancer patients nor in the healthy controls. The depression of NK activity did not correlate with the localisation of the tumour, patient's age or body weight reduction. The defective NK activity of PBMC from MN cancer patients was restored to normal by rIL-2, but not by alfa-rIFN. Parenteral nutrition of MN patients with the proper amount of proteins and calories quickly corrected the depressed NK activity, indicating a central role of malnutrition in the genesis of their immune disfunction. PBMC from MN cancer patients produced lower amounts of IL-2, as compared with healthy controls, when stimulated in vitro; the most frequently affected were the responses to recall antigens such as influenza virus vaccine (FLU), while those to allogeneic PBMC (ALLO) and phytohaemagglutinin (PHA) were less affected. However, for each patient the ability to produce IL-2 in vitro did not correlate with NK activity, thus showing how the impairment of NK activity is not subsequent to a decreased production of endogenous IL-2. In summary, it can be concluded that malnutrition, rather than malignancy, plays a major role in the immune dysfunction of cancer patients.

Highlights

  • Purified human recombinant IL-2 was provided by the Biogen (Cambridge, MA); recombinant human Interferon alfa 2a was provided by Roche (Basel, CH); anti-TAC and fluorescinated anti-Leu.7 monoclonal antibodies (MoAB) were from Becton Dickinson (Sunnyvale, CA)

  • This clearly indicates that the Natural killer (NK) activity was depressed in the great majority of MN while it was normal in WN cancer patients

  • The number of NK cells was evaluated by the MoAb anti-Leu.7, which reacts with NK cells together with a variable proportion of CD3 +, CD8 + T lymphocytes

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Summary

Introduction

Purified human recombinant IL-2 (rIL-2) was provided by the Biogen (Cambridge, MA); recombinant human Interferon alfa 2a (alfa-rIFN) was provided by Roche (Basel, CH); anti-TAC and fluorescinated anti-Leu. monoclonal antibodies (MoAB) were from Becton Dickinson (Sunnyvale, CA). The patients were hospitalised at the Istituto nazionale Tumori of Milano (1987-1989) for cancer of various localisations. Patients exhibiting a documented reduction of the usual body weight of 10-20% in about 6 months, were admitted to the study. A group of 37 healthy males and females, aged from 25 to 65, taken from blood donors of the Istituto nazionale Tumori, was evaluated as the second control group. The characteristics of malnourished (MN) and well-nourished (WN) patients were as follows: WN cancer patients 20 subjects (14 males and six females) aged from 41 to 70. MN cancer patients 39 subjects (27 males and 12 females) aged from 41 to 89. The immune parameters of a group of ten MN cancer patients, which underwent parenteral nutrition, were evaluated both prior and after the 10 day treatment period. Cells were resuspended in RPMI 1640 (Gibco, Grand Island, NY) containing 1% glutamine

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