Patients with lung cancer often display impaired immunity,^1–10) including low counts of T-lymphocytes, and these impairments have been postulated to be significant in the development and progression of lung cancer, and the nutritional status of patients has been contributed to immunologic abnormalities⁴⁾.

Recently, Wesselius et al.⁴⁾ have reported on lymphocyte subsets in patients with untreated lung cancer, and we also have reported on T lymphocyte subsets in patients with untreated lung cancer.¹⁰⁾ But most studies, including our previous study¹⁰⁾, have evaluated only untreated cases.

In the present study, we undertook to further evaluate the changes of peripheral T lymphocyte subsets in patients with lung cancer following treatment (anticancer chemotherapy and pulmonary resection).

There are many reports that patients with lung cancer often display immune abnormalities,^{1–10,13,14,18)} and these abnormalities in cell mediated immunity have been considered to be significant in the development and progression of lung cancer^{1,4,9,15,16,20,21,23)}.

Evaluation of immunocompetence in patients with lung cancer by peripheral total lymphocyte counts,^1,4,8–10) percentage of lymohocytes,³⁾ delayed skin hypersensitivity test,^{6,10,20,21,23)} quantitation of peripheral lymphocyte subsets^{4,5,7,9,10,12)} and mitogen stimulation of lymphocytes^2,8) has demonstrated both functional and quantitative abnormalities.

However, conflicting data have been reported on the distribution of mononuclear cell populations in patients with lung cancer^{3–10,11,16,19,22)}.

In the present study, we evaluated the distribution of peripheral T lymphocyte subsets in patients with untreated lung cancer and changes of T lymphocyte subsets following treatment (pulmonary resection or chemotherapy).

The present investigation revealed that patients with untreated lung cancer had increased total WBC counts in stage I or II NSCLC (esp. squamous cell cancer) compared to normal controls, which were significantly decreased after operation and were also noted in responders. Olkowski et al.³⁾ and Dellon et al.¹⁶⁾ found that patients with lung cancer had increased WBC counts, especially in adenocarcinoma, but our study revealed this in squamous cell cancer and we considered that it may be due to distal bronchial obstruction causing inflammation or a pneumonic process.

Patients with untreated lung cancer had significantly decreased percentages and absolute counts of peripheral lymphocytes compared to normal controls, which were more apparent in stage III NSCLC, SCLC (esp. ED) and squamous cell type, but these abnormalities were not changed or improved after treatment.

The nonresponder group had a significant decrease in lymphocyte counts compared to responders before treatment, and had a decrease in percentage and absolute counts of lymphocytes compared to normal controls before and after treatment. We suggest that patients with initial (untreated) lower lymphocyte counts may be possible nonresponders following treatment.

We found that patients with advanced lung cancer had decreased lymphocyte counts, and this finding is in accord with other results^{1,3,4,7,8,10)}.

Roberts et al.¹⁾ reported that lymphopenia was a feature of patients with metastatic disease of bronchial carcinoma. Krant et al.⁶⁾ found that circulating lymphocytes were decreased significantly during the months approaching death.

Patients with untreated lung cancer had a significant decrease in OKT8(%) compared to normal controls, and this was decreased in patients with SCLC (esp. ED) and all stages of NSCLC (esp. squamous and adenocarcinoma).

These results are in discord with other results,^4,5,7,12) but we confirmed our previous study.¹⁰⁾ Ginns et al.²³⁾ reported that patients with squamous cell cancer involving lymph nodes (N1 or N2 disease) had a decrease in numbers and percentage of T8 lymphocytes. Because our treated NSCLC cases consisted mainly of squamous cell cancer, decreased OKT8(%) is considered to be consistent with Ginns et al.²³⁾ Gross et al.⁸⁾ found that a decrease in circulating rosette-forming cells was predictive of carcinoma in undiagnosed pulmonary coin lesion. However, Jansen et al.¹³⁾ and Lichtenstein et al.¹⁴⁾ have reported that there were no abnormalities of circulating T cells in patients with lung cancer. Recently, Wesselius et al.⁴⁾ reported that patients with SCLC and advanced NSCLC had a significant decrease in the number of T4 and T8 cells.

In any case, regardless of whether or not T cell subsets had changed, we consider that these changes would be due to methodologic differences⁵⁾, compartmentalization into lungs¹¹⁾ or clonal expansion.

Patients with untreated lung cancer had a significant increase in the OKT4/OKT8 ratio compared to normal controls, which was noted in adenocarcinoma and stage II NSCLC, and was considered to be due to the decrease in OKT8(%).

The significance of this finding is open to speculation, but this result is the same as those of other studies.^5,10)

After treatment, the decreased OKT8(%) before treatment returned to the normal range in patients with stage I or II NSCLC, but remained persistently decreased in stage III and nonresponders. So, we suggest that patients with advanced lung cancer having low lymphocyte counts before treatment and decreased OKT8(%) after therapy might not be responsive to treatment.

The increased OKT4/OKT8 ratio in stage III NSCLC returned to the normal range, and this finding suggests that immunoabnormalities in patients with lung cancer might be improved following treatment with or without response.

In summary, patients with lung cancer had immunologic abnormalities, such as decreased lymphocyte counts, decreased OKT8(%) and increased OKT4/OKT8 ratios, and these abnormalities might be improved following treatment.

Further data monitoring the quantitative and functional changes (esp. for SCLC) of lymphocytes following treatment (including radiotherapy) are needed to analyse the role of immunologic changes for the progression, recurrence and prognosis of lung cancer.