Concomitant Active Tuberculosis Prolongs Survival in Non-Small Cell Lung Cancer: A Study in a Tuberculosis-Endemic Country

BACKGROUND: Adjuvant tumor cell vaccine with chemotherapy against non-small cell lung cancer (NSCLC) shows limited clinical response. Whether it provokes effective cellular immunity in tumor microenvironment is questionable. Concomitant active tuberculosis in NSCLC (TBLC) resembles locoregional immunotherapy of tumor cell vaccine; thus, maximally enriches effective anti-tumor immunity. This study compares the survival and immunological cell profile in TBLC over NSCLC alone. METHODS: Retrospective review of NSCLC patients within 1-year-period of 2007 and follow-up till 2010. RESULTS: A total 276 NSCLC patients were included. The median survival of TBLC is longer than those of NSCLC alone (11.6 vs. 8.8 month, p<0.01). Active tuberculosis is an independent predictor of better survival with HR of 0.68 (95% CI, 0.48 ~ 0.97). Squamous cell carcinoma (SCC) (55.8 vs. 31.7%, p<0.01) is a significant risk factor for NSCLC with active TB. The median survival of SCC with active tuberculosis is significantly longer than adenocarcinoma or undetermined NSCLC with TB (14.2 vs. 6.6 and 2.8 months, p<0.05). Active tuberculosis in SCC increases the expression of CD3 (46.4 ± 24.8 vs. 24.0 ± 16.0, p<0.05), CXCR3 (35.1 ± 16.4 vs. 19.2 ± 13.3, p<0.01) and IP-10 (63.5 ± 21.9 vs. 35.5 ± 21.0, p<0.01), while expression of FOXP3 is decreased (3.5 ± 0.5 vs. 13.3 ± 3.7 p<0.05, p<0.05). Survival of SCC with high expression of CD3 (12.1 vs. 3.6 month, p<0.05) and CXCR3 (12.1 vs. 4.4 month, p<0.05) is longer than that with low expression. CONCLUSIONS: Active tuberculosis in NSCLC shows better survival outcome. The effective T lymphocyte infiltration in tumor possibly underlies the mechanism. Locoregional immunotherapy of tumor cell vaccine may deserve further researches

Survival outcome analysis of high or low immunohistochemical marker indices divided by median in squamous cell carcinoma.

<p>Survival outcome analysis of high or low immunohistochemical marker indices divided by median in squamous cell carcinoma.</p

Analysis of clinical factors associated with active tuberculosis in NSCLC patients.

<p>*comparison of squamous vs. non-squamous cell carcinoma</p><p>**(ORs 2.09; 95% CI, 1.06∼4.14, <i>p</i>< 0.05) by multivariate logistic regression test</p><p>NSCLC: non-small cell lung cancer, BSC: best supportive care, TB: tuberculosis.</p

Kaplan-Meier survival curve of (A) NSCLC with active TB grouped by histology (log rank test, <i>p</i><0.05).

<p>(B) NSCLC without TB grouped by histology (log rank test, <i>p</i> = 0.27). Green line: SCC, Blue line: adenocarcinoma, Yellow line: undetermined NSCLC. SCC: squamous cell carcinoma NSCLC: non-small cell lung cancer</p

Immunohistochemical marker indices of squamous cell carcinoma with or without active tuberculosis.

<p>TB: tuberculosis.</p

Predicting factors of survival outcome by univariate and multivariate analysis.

<p>NSCLC: non-small cell lung cancer, HR: hazard ratio, BSC: best supportive care, TB: tuberculosis.</p

Kaplan-Meier survival curve of lung cancer patients with and without active tuberculosis (log rank test, <i>p</i><0.01)

<p>. Green line: patients with TB. Blue line: patients without TB.</p

Baseline patients characteristics (N = 276).

<p>NSCLC: non-small cell lung cancer.</p><p>BSC: best supportive care, TB: tuberculosis.</p

Representative image of immunohistochmical stain demonstrating immunological markers with high and low expression respectively for CD3 (A) (B), CXCR3 (C) (D), and FOXP3 (E) (F)

<p>. Magnification×400.</p