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 we sought to investigate the ability of tumor infiltrating immune cells (TIICs) to express HLA-DR antigen in the primary tumor site and reactive regional lymph nodes (LNs) in non small cell lung cancer (NSCLC).


METHODS
Material consisting of 60 NSCLCs with corresponding regional LNs was studied by immunohistochemistry for human leukocyte antigen D-region related (HLA-DR) expression. Control reactive LNs, regional to several different malignant and non-malignant disorders, were also included in the study.


RESULTS
Primary tumor site investigation revealed positive HLA-DR cancer cells in 22% of cases, whereas TIICs rarely expressed HLA-DR antigens. The lack of HLA-DR expression in TIICs was gradually attenuated as the distance from the primary tumor site decreased. Regional LN investigation showed that all follicles (paracapsular and deep cortical ones) were HLA-DR-negative in 60% of the LNs; in the remaining 40%, the paracapsular follicles remained 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 negative. All control reactive LNs, regional to several distinct malignant and non-malignant disorders, were found to be HLA-DR-positive.


CONCLUSIONS
The impairment of HLA-DR expression, detected both in neoplastic and by-stander immune cells, may justify the immunosuppression observed in NSCLC. This phenomenon may be due to a putative soluble factor in the tumor environment secreted by cancer cells.
Foukas
P G
PG
Department of Histology and Embryology, Medical School, University of Athens, Greece.
Tsilivakos
V
V
Zacharatos
P
P
Mariatos
G
G
Moschos
S
S
Syrianou
A
A
Asimacopoulos
P J
PJ
Bramis
J
J
Fotiadis
C
C
Kittas
C
C
Gorgoulis
V G
VG
D002289:Carcinoma, Non-Small-Cell Lung / Q000276:immunology* / Q000378:metabolism; D006684:HLA-DR Antigens / Q000096:biosynthesis / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology; D007150:Immunohistochemistry; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism; D008175:Lung Neoplasms / Q000276:immunology* / Q000378:metabolism; D008198:Lymph Nodes / Q000276:immunology / Q000378:metabolism; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology* / Q000378:metabolism; D008264:Macrophages / Q000276:immunology / Q000378:metabolism
D006684:HLA-DR Antigens