Expression of HLA-DR is reduced in tumor infiltrating immune cells (TIICs)and regional lymph nodes of non-small-cell lung carcinomas. A putative mechanism of tumor-induced immunosuppression?

Background: Deregulation of MHC class II molecules consists of a favorable mechanism of tumor evasion from immune surveillance. Among these molecules. HLA-DR antigens are the predominant ones in cancer. In the present study w e sought to investigate the ability of tumor infiltrating immune cells (TII Cs) to express HLA-DR antigen in the primary tumor site and reactive region al lymph nodes (LNs) in non small cell lung cancer (NSCLC). Materials and M ethods: Material consisting of 60 NSCLCs with corresponding regional LNs wa s studied by immunohistochemistry for human leukocyte antigen D-region rela ted (HLA-DR) expression. Control reactive LNs, regional to several differen t malignant and non-malignant disorders, were also included in the study. R esults: Primary tumor site investigation revealed positive HLA-DR cancer ce lls in 22% of cases, whereas TIICs rarely expressed HLA-DR antigens. The la ck of HLA- DR expression in TIICs was gradually attenuated as the distance from the primary tumor site decreased. Regional LN investigation showed tha t all follicles (paracapsular and deep cortical ones) were HLA-DR-negative in 60% of the LNs; in the remaining 40%, the paracapsular follicles remaine d negative, while all deep cortical ones were positive. Interestingly, LNs possessing only HLA-DR-negative follicles were more proximal to the primary tumor site compared to those that had only the paracapsular follicles nega tive. All control reactive LNs, regional to several distinct malignant and non-malignant disorders, were found to be HLA-DR positive. Conclusion: The impairment of HLA-DR expression, detected both in neoplastic and by-stander immune cells, may justify the immunosuppression observed in NSCLC. This ph enomenon may be due to a putative soluble factor in the tumor environment s ecreted by cancer cells.