Abstract
BACKGROUND—For patients with non-small cell lung cancer the TNM staging system and other conventional prognostic factors fail to predict accurately the outcome of treatment and survival. This study attempts to determine the prognostic value for survival of the proportions of CD4+ lymphocytes in the pleural cavity (PLY) of patients with resectable non-small cell lung cancer. METHODS—Lymphocytes in the pleural cavity separated from 51 patients with non-small cell lung cancer were examined by flow cytometry to measure the proportions of CD4+ PLY. Univariate and multivariate analyses were performed to assess the association between the proportion of CD4+ PLY and survival. RESULTS—The 5 year survival rate of patients with percentage CD4+ PLY of ⩽30% was 84% whereas that of patients with %CD4+ PLY >30% was 26.9%. The difference in survival between the %CD4+ PLY ⩽30% and %CD4+ PLY >30% groups was significant (p<0.0001). The %CD4+ PLY in those who survived for 5 years was significantly lower than that in the patients who died within 5 years (p<0.0001). The difference in survival between patients with stage IA and IB lung cancer with %CD4+ PLY ⩽30% and those with %CD4+ PLY >30% was also significant (p =0.015). Multivariate analysis showed that the proportion of CD4+ PLY (hazard ratio=6.9, 95% CI 0.045to 0.47) and nodal status (hazard ratio=22.7, 95% CI 0.006 to 1.806) are significant and independent prognostic factors for the survival of patients with lung cancer. CONCLUSIONS—The proportion of CD4+ PLY may help to select patients who are likely to have a poorer prognosis after surgery and therefore may be suitable for consideration of adjuvant treatments. These results need confirmation in a larger prospective study.
Full Text
The Full Text of this article is available as a PDF (125.9 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Albera C., Mabritto I., Ghio P., Scagliotti G. V., Pozzi E. Lymphocyte subpopulations analysis in pleural fluid and peripheral blood in patients with lymphocytic pleural effusions. Respiration. 1991;58(2):65–71. doi: 10.1159/000195899. [DOI] [PubMed] [Google Scholar]
- Burger U. L., Chang M. P., Goedegebuure P. S., Eberlein T. J., Adams-Hodgins S. Recruitment of host CD8+ T cells by tumor-infiltrating lymphocytes and recombinant interleukin-2 during adoptive immunotherapy of cancer. Surgery. 1995 Mar;117(3):325–333. doi: 10.1016/s0039-6060(05)80209-0. [DOI] [PubMed] [Google Scholar]
- Chin Y., Janseens J., Vandepitte J., Vandenbrande J., Opdebeek L., Raus J. Phenotypic analysis of tumor-infiltrating lymphocytes from human breast cancer. Anticancer Res. 1992 Sep-Oct;12(5):1463–1466. [PubMed] [Google Scholar]
- Chretien J. Quelques aspects immunologiques des maladies de la plèvre. Presse Med. 1970 Apr 22;78(20):921–925. [PubMed] [Google Scholar]
- Gemignani M., Maiman M., Fruchter R. G., Arrastia C. D., Gibbon D., Ellison T. CD4 lymphocytes in women with invasive and preinvasive cervical neoplasia. Gynecol Oncol. 1995 Dec;59(3):364–369. doi: 10.1006/gyno.1995.9961. [DOI] [PubMed] [Google Scholar]
- Goedegebuure P. S., Eberlein T. J. The role of CD4+ tumor-infiltrating lymphocytes in human solid tumors. Immunol Res. 1995;14(2):119–131. doi: 10.1007/BF02918172. [DOI] [PubMed] [Google Scholar]
- Greenstein A., Pecht M., Kaver I., Trainin N., Braf Z. Characterization of peripheral blood T-cell subpopulation of bladder cancer patients. Urol Res. 1991;19(4):219–222. doi: 10.1007/BF00305298. [DOI] [PubMed] [Google Scholar]
- Hausheer F. H., Yarbro J. W. Diagnosis and treatment of malignant pleural effusion. Semin Oncol. 1985 Mar;12(1):54–75. [PubMed] [Google Scholar]
- Inoue Y., Shijubo N., Uede T. Induction of killer cells from lymphocytes in pleural effusion of advanced lung cancer patients. Jpn J Cancer Res. 1990 Oct;81(10):1012–1020. doi: 10.1111/j.1349-7006.1990.tb03339.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kaver I., Pecht M., Trainin N., Greenstein A., Braf Z. T lymphocyte subsets and function in the peripheral blood of patients with urological cancer. Oncology. 1992;49(2):108–113. doi: 10.1159/000227022. [DOI] [PubMed] [Google Scholar]
- Lacki J., Markowska J., Wiktorowicz K. Phenotype of lymphocyte in ovarian tumor peritoneal fluid. A preliminary study. Eur J Gynaecol Oncol. 1992;13(6):475–479. [PubMed] [Google Scholar]
- Lee K. Y., Goedegebuure P. S., Linehan D. C., Eberlein T. J. Immunoregulatory effects of CD4+ T helper subsets in human melanoma. Surgery. 1995 Apr;117(4):365–372. doi: 10.1016/s0039-6060(05)80054-6. [DOI] [PubMed] [Google Scholar]
- Lucivero G., Pierucci G., Bonomo L. Lymphocyte subsets in peripheral blood and pleural fluid. Eur Respir J. 1988 Apr;1(4):337–340. [PubMed] [Google Scholar]
- Markowska J., Lacki J. K., Jaroszewski J., Wiktorowicz K. The usefulness of CD4/CD8 ratio evaluation in monitoring of ovarian cancer patients. Eur J Gynaecol Oncol. 1995;16(1):54–58. [PubMed] [Google Scholar]
- Mulder W. M., Stukart M. J., Roos M., van Lier R. A., Wagstaff J., Scheper R. J., Bloemena E. Culture of tumour-infiltrating lymphocytes from melanoma and colon carcinoma: removal of tumour cells does not affect tumour-specificity. Cancer Immunol Immunother. 1995 Nov;41(5):293–301. doi: 10.1007/BF01517217. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nakahashi H., Yasumoto K., Nagashima A., Yaita H., Takeo S., Motohiro A., Furukawa T., Inokuchi K., Nomoto K. Antitumor activity of macrophages in lung cancer patients with special reference to location of macrophages. Cancer Res. 1984 Dec;44(12 Pt 1):5906–5909. [PubMed] [Google Scholar]
- Peto R., Pike M. C. Conservatism of the approximation sigma (O-E)2-E in the logrank test for survival data or tumor incidence data. Biometrics. 1973 Sep;29(3):579–584. [PubMed] [Google Scholar]
- Pettersson T., Klockars M., Hellström P. E., Riska H., Wangel A. T and B lymphocytes in pleural effusions. Chest. 1978 Jan;73(1):49–51. doi: 10.1378/chest.73.1.49. [DOI] [PubMed] [Google Scholar]
- Roussel E., Gingras M. C., Grimm E. A., Roth J. A. High expression of adhesion molecules/activation markers with little interleukin-2, interferon gamma, and tumor necrosis factor beta gene activation in fresh tumor-infiltrating lymphocytes from lung adenocarcinoma. Cancer Immunol Immunother. 1995 Jul;41(1):1–9. doi: 10.1007/BF01788953. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schöndorf T., Engel H., Lindemann C., Kolhagen H., von Rücker A. A., Mallmann P. Cellular characteristics of peripheral blood lymphocytes and tumour-infiltrating lymphocytes in patients with gynaecological tumours. Cancer Immunol Immunother. 1997 Apr;44(2):88–96. doi: 10.1007/s002620050360. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Shields T. W. The significance of ipsilateral mediastinal lymph node metastasis (N2 disease) in non-small cell carcinoma of the lung. A commentary. J Thorac Cardiovasc Surg. 1990 Jan;99(1):48–53. [PubMed] [Google Scholar]
- Shimokata K., Saka H., Murate T., Hasegawa Y., Hasegawa T. Cytokine content in pleural effusion. Comparison between tuberculous and carcinomatous pleurisy. Chest. 1991 May;99(5):1103–1107. doi: 10.1378/chest.99.5.1103. [DOI] [PubMed] [Google Scholar]
- Sone S., Nakanishi M., Ohmoto Y., Yanagawa H., Ogura T. Macrophage colony-stimulating factor activity in malignant pleural effusions. Its augmentation by intrapleural interleukin-2 infusions. Chest. 1991 Feb;99(2):377–381. doi: 10.1378/chest.99.2.377. [DOI] [PubMed] [Google Scholar]
- Takahashi K., Sone S., Kimura S., Ogura T., Monden Y. Phenotypes and lymphokine-activated killer activity of pleural cavity lymphocytes of lung cancer patients without malignant effusion. Chest. 1993 Jun;103(6):1732–1738. doi: 10.1378/chest.103.6.1732. [DOI] [PubMed] [Google Scholar]
- Takahashi K., Sone S., Saito S., Kamamura Y., Uyama T., Ogura T., Monden Y. Granulocyte-macrophage colony-stimulating factor augments lymphokine-activated killer activity from pleural cavity mononuclear cells of lung cancer patients without malignant effusion. Jpn J Cancer Res. 1995 Sep;86(9):861–866. doi: 10.1111/j.1349-7006.1995.tb03097.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Yanagawa H., Sone S., Nii A., Fukuta K., Nakanishi M., Maeda K., Honda M., Ogura T. Lymphokine-activated killer induction and its regulation by macrophages in malignant pleural effusions. Jpn J Cancer Res. 1989 Dec;80(12):1220–1227. doi: 10.1111/j.1349-7006.1989.tb01658.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Yasumoto K., Mivazaki K., Nagashima A., Ishida T., Kuda T., Yano T., Sugimachi K., Nomoto K. Induction of lymphokine-activated killer cells by intrapleural instillations of recombinant interleukin-2 in patients with malignant pleurisy due to lung cancer. Cancer Res. 1987 Apr 15;47(8):2184–2187. [PubMed] [Google Scholar]
- Yoshino I., Yano T., Murata M., Miyamoto M., Ishida T., Sugimachi K., Kimura G., Nomoto K. Phenotypes of lymphocytes infiltrating non-small cell lung cancer tissues and its variation with histological types of cancer. Lung Cancer. 1993 Oct;10(1-2):13–19. doi: 10.1016/0169-5002(93)90305-h. [DOI] [PubMed] [Google Scholar]