Expression of cancer-testis antigens MAGE-A3/6 and NY-ESO-1 in non-small-cell lung carcinomas and their relationship with immune cell infiltration.

Cancer-testis antigens (CTAs) are expressed only in many cancers and limited immunoprivileged sites such as the testis and placenta. Dendritic cells (DCs) and CD8+ T lymphocytes (CTLs) play roles in the immune responses to tumor growth and may affect the prognosis of cancers. This study was designed to investigate the clinicopathologic significance of CTA expression in non-small-cell lung carcinomas (NSCLCs) and its relationship with immune cells. Immunohistochemical staining to CTAs such as MAGE-A3/6 and NY-ESO-1 was performed using paraffin blocks from 132 cases of NSCLCs, including 75 cases of squamous cell carcinoma (SqCC) and 57 cases of adenocarcinoma (AdC), and the results were evaluated to correlate with tumor-infiltrating DCs and CTLs and clinicopathologic features. MAGE-A3/6 and NY-ESO-1 were expressed in 50.0% (66/132) and 18.2% (24/132) of NSCLCs, respectively. MAGE-A3/6 was expressed more frequently in SqCC than in AdC, but the expression of NY-ESO-1 showed no difference in both types. CTAs revealed a higher expression in male than in female. In advanced stage III, NY-ESO-1-positive patients showed poorer survival than NY-ESO-1-negative patients. Otherwise, the CTA expression did not correlate with clinicopathologic parameters. No relationship was found between DC and CTL infiltration in all NSCLCs. Regarding DC infiltration, the group showing negative expression to CTAs displayed an even higher number of infiltrating DCs than those showing positivity to one or the other or both CTAs. Although the aberrant expression of MAGE-A3/6 and NY-ESO-1 in NSCLC did not directly influence clinical prognostic factors, the higher expression of MAGE-A3/6 in SqCC suggests its value as a potential target for immunotherapy in this type of NSCLC. The inverse relationship between DCs and CTA expression may indicate that CTA-positive tumor cells would be akin to tumor stem cells escaping host immune response.