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Defective cytostatic activity of pulmonary alveolar macrophages in primary lung cancer
1Department of Respiratory Medicine, Prince Henry's Hospital, Melbourne, Australia.
Abstract:
Macrophages are thought to play an important immune effector cell role in antitumor host defense. It remains unclear whether PAM antitumor activity in patients with lung cancer is normal or impaired. We examined PAM cytostasis in patients with lung cancer and in control subjects and determined whether the in vitro PAM response could be enhanced by gamma-interferon. Nineteen patients with primary lung carcinoma and 15 control patients underwent BAL. Five patients with cancer underwent lavage of both lungs to assess whether any abnormality found related to tumor proximity or was part of a more generalized defect. Cytostatic activity was assessed by measuring inhibition of incorporation of tritiated thymidine into the target cell U937. There was a significant difference in baseline cytostatic activity between patients with cancer (mean +/- SE, 59 +/- 7 percent) and control patients (92 +/- 2 percent) (p less than 0.0002). The increase in cytostatic function after stimulation with gamma-interferon (1,250 units/ml) was higher in the group with cancer (28 +/- 5 percent increase from baseline) than in controls (5 +/- 1 percent) (p less than 0.0005). Cytostasis after stimulation was not significantly different between the groups. In the bilaterally lavaged group, baseline cytostatic activity was not different between cancerous and noncancerous lungs and was again significantly lower than in control subjects. These results indicate (a) that PAM baseline cytostatic activity in patients with cancer is lower than in controls, (b) that gamma-interferon can significantly augment cytostatic function in patients with cancer, to levels comparable with those achievable in control patients, and (c) that the PAM abnormality is part of a generalized immune defect in lung cancer and does not simply reflect a local response to the carcinoma. It may be inferred from these results that PAMs from patients with primary lung cancer are not fully stimulated in vivo and that a defect of T cell lymphokine production may underlie the macrophage dysfunction.
Insights
Pulmonary alveolar macrophages (PAMs) show impaired antitumor activity in lung cancer patients. Gamma-interferon boosts this function, suggesting a generalized immune defect in lung cancer.
Area of Science:
- Immunology
- Oncology
Background:
- Macrophages are crucial immune effector cells in antitumor defense.
- The function of pulmonary alveolar macrophages (PAMs) in lung cancer patients is not well understood.
Purpose of the Study:
- To investigate the cytostatic activity of PAMs in lung cancer patients.
- To determine if gamma-interferon can enhance PAM antitumor function in these patients.
Main Methods:
- Bronchoalveolar lavage (BAL) was performed on 19 lung cancer patients and 15 controls.
- PAM cytostatic activity was measured by assessing inhibition of tritiated thymidine incorporation into U937 cells.
- The effect of gamma-interferon stimulation on PAM function was evaluated.
Main Results:
- Patients with lung cancer exhibited significantly lower baseline PAM cytostatic activity (59%) compared to controls (92%).
- Gamma-interferon significantly increased PAM cytostatic function in cancer patients (28% increase) compared to controls (5% increase).
- Stimulated PAM cytostasis levels were comparable between cancer patients and controls.
Conclusions:
- PAM baseline antitumor activity is impaired in lung cancer patients.
- Gamma-interferon can effectively enhance PAM function in lung cancer.
- The observed PAM dysfunction is a generalized immune defect, not a localized tumor response, possibly due to T cell lymphokine production defects.