Changes in the
human leukocyte antigen (HLA) class I expression and
cytokine and
chemokine production both by
cancer cells and by normal surrounding tissue are believed to be responsible for immune escape and
tumor progression. In this study, we compared the
tumor expression levels of HLA heavy chain (HLAhc), beta-2-microglobulin (beta2m),
chemokines (
Interferon-gamma-inducible
Protein-10 (IP-10),
Interferon-inducible T-cell Alpha-
Chemoattractant (I-TAC),
Stromal cell-Derived Factor-1 (SDF-1),
Macrophage Inflammatory Protein-1-alpha (MIP-1-alpha) and Regulated upon Activation, Normally T-Expressed, and presumably Secreted (
RANTES)) and
cytokines (
Vascular Endothelial Growth Factor (
VEGF),
Interferon-gamma (IFN-gamma),
Interleukin-10 (IL-10),
Tumor Growth Factor-beta (TGB-beta)) in primary
tumors and adjacent normal tissues from patients with localized and metastatic
renal cell carcinoma (RCC) using a quantitative real-time polymerase chain reaction technique. We report that the expression of HLAhc, beta2m and the studied
cytokines and
chemokines (except for SDF-1) was significantly higher in the
tumor (29 samples) than in the normal tissue (14 samples). When we compared the
tumor expression levels between patients with localized RCC and patients with advanced metastatic stage, we found that the
messenger RNA expression levels of HLAhc and beta2m were much lower in patients with metastatic RCC (6 cases) than in patients with localized
cancer (23 cases), with levels similar to those in normal tissue. This was also confirmed on a
protein level by immunohistological labeling of
tumor tissues. Thirty-nine percent of the analyzed RCC
tumors showed partial loss of HLA class I molecules, while 6% of the
tumors showed HLA class I total loss. The expression of IP-10, SDF-1 and
VEGF-c was also significantly lower in patients with advanced
tumor, while the IFN-gamma expression in metastatic RCC was not detectable. Our findings show that primary RCC
tumors are characterized by a high expression of HLAhc and a presence of proinflammatory mediators and
chemokines. We also observed that
disease progression and development of
metastasis in RCC are associated with decreased expression of HLAhc, beta2m, IP-10, SDF-1 and IFN-gamma. This microenvironment may suppress the cytotoxic response, creating conditions that favor tumor escape and
cancer progression.