HLA class I and chemokine gene expression in renal cell carcinomas

Immune mechanisms have been suggested to play a role in the natural disease course of RCC. The objective of this study was to examine factors that may be involved in the significant survival benefit of immunotherapy for RCC patients. A low frequency of total or HLA haplotype loss was found and, in parallel, the tumour tissue expressed more HLA classI/B2m mRNA. These data significantly differ from those reported in other epithelial tumours. Furthermore, chemokines and their receptors play key roles in leukocyte trafficking and are also implicated in cancer metastasis. We identified a number of chemokines that were highly expressed in RCC versus normal tissue. RT-PCR analysis showed expression of antiangiogenic agents I-TAC and IP-10, and proinflammatory chemokines MIP-1a and RANTES in RCC tissues and very weak or undetectable expression in most of the normal kidney tissues. In contrast, the angiogenic SDF-1 was more strongly detected in the normal tissue. This chemokine production pattern was correlated with a preferential recruitment of CD4+ Th1-polarized effector memory cells that express CXCR3/CCR5, monocytes and NK cells. The composition of the tumour infiltrate was different in more advanced tumours. In conclusion, upregulation of HLA class I gene expression in addition to chemokine expression in the tumour environment may contribute to the successful response of RCC to immunotherapy.