AI Article Synopsis
- Small cell lung cancer (SCLC) often spreads rapidly, but some patients with paraneoplastic syndrome remain in limited-stage disease (LD) due to immune responses against tumor-related antigens.
- A study analyzed T cells from 35 SCLC patients, finding that those in LD had more immune effector T cells (Teff) compared to those in extended-stage disease (ED).
- The findings suggest that a high ratio of Teff to regulatory T cells (Treg) in LD-SCLC patients may serve as a biomarker for different stages of the disease and highlight the need to enhance Teff cells, especially Th17, to prevent disease spread.
Article Abstract
Purpose: Small cell lung cancer (SCLC) possesses high tendency to disseminate. However, SCLC patients with paraneoplastic syndrome mediated by immunity against onconeural antigens remain in limited-stage disease (LD) without distant metastases. Cumulative evidence regulates that a balance between immune and regulatory T (Treg) cells determines the magnitude of immune responses to not only self-antigens but also tumor-associated antigens. The purpose of this study was to elucidate the immunologic balance induced in SCLC patients.
Experimental Design: We analyzed T cells in the peripheral blood of 35 consecutive SCLC patients, 8 long-term survivors, and 19 healthy volunteers.
Results: Purified CD4(+) T cells with down-regulated expression of CD62L (CD62L(low)) produced IFN-gamma, interleukin (IL)-4, and IL-17, thus considered to be immune effector T cells (Teff). Significantly more Teff cell numbers were detected in LD-SCLC patients than that of extended-stage SCLC (ED-SCLC). By contrast, induction of CD62L(high)CD25(+) CD4(+) Treg cells was significantly higher in ED-SCLC patients. Long-term survivors of SCLC maintained a high Teff to Treg cell ratio, whereas patients with recurrent disease exhibited a low Teff to Treg cell ratio. Teff cells in LD-SCLC patients included more IL-17-producing CD4(+) T cells (Th17). Moreover, dendritic cells derived from CD14(+) cells of LD-SCLC patients secreted more IL-23.
Conclusion: These results show that CD4(+) T-cell balance may be a biomarker that distinguishes ED-SCLC from LD-SCLC and predicts recurrence. This study also suggests the importance of inducing Teff cells, particularly Th17 cells, while eliminating Treg cells to control systemic dissemination of SCLC.
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| http://dx.doi.org/10.1158/1078-0432.CCR-08-1156 | DOI Listing |
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