HLA Class I Expression on Human Ovarian Carcinoma Cells Correlates with T-Cell Infiltrationin Vivoand T-Cell Expansionin Vitroin Low Concentrations of Recombinant Interleukin-2

Abstract

This study was carried out to determine whether HLA class I or class II expression on ovarian tumor cells and lymphocytic infiltration of the epithelial ovarian carcinoma (EOC) tissues were responsible for the ability to expand tumor-infiltrating lymphocytes (TIL)in vitroin low concentrations of recombinant interleukin-2 (rIL-2). Immunohistochemical analysis was performed using monoclonal antibodies that recognize framework determinants of either HLA class I or HLA class II or leukocyte differentiation antigens (LCA, CD3, CD4, and CD8). Cryostat sections of EOC had HLA class I and HLA class II expression on at least 5% of tumor cells in 18 of 20 specimens (90%). From another portion of the same tumor specimens T-cell lines were developed from TIL in low concentrations of rIL-2 (200–600 IU/ml) in 7 of 17 patients. Tumors from which TIL were expandedin vitrowith rIL-2 had significantly higher proportions of HLA class I-positive tumor cells (73 ± 10%) compared to tumors from which TIL failed to grow (40 ± 10%) (P= 0.036). However, there was no difference in the proportions of HLA class II-positive tumor cells between the two groups. Tumor specimens of patients whose TIL were expanded in rIL-2 had significantly higher numbers per field (423 ± 114 vs 154 ± 20;P= 0.005) and proportions (90 ± 3% vs 77 ± 4%;P= 0.023) of infiltrating CD3+cells, significantly higher numbers per field (115 ± 44 vs 19 ± 5;P= 0.003) and proportions (25 ± 5% vs 11 ± 2%;P= 0.017) of CD8+cells and significantly higher numbers per field of CD4+cells (318 ± 101 vs 113 ± 18;P= 0.025), in comparison to tumor specimens from patients whose TIL did not growin vitro.Significant correlations were observed between the proportions of HLA class I-positive EOC tumor cells and the numbers of infiltrating LCA-positive cells (r= 0.67;P= 0.005) CD3+cells (r= 0.70;P= 0.002), CD4+cells (r= 0.69;P= 0.003), and CD8+cells (r= 0.82;P= 0.001). The proportions of HLA class II-positive tumor cells correlated positively (r= 0.45;P= 0.049) only with the numbers of CD8+-infiltrating cells. In conclusion, we report here that HLA class I expression on EOC cells correlates with T-cell infiltrationin vivoand T-cell expansionin vitro,in low concentrations of rIL-2.