INTRODUCTION: NK cell deficiencies (NKD) are a subset of primary immunodeficiency diseases (PIDD). Functional NKD (fNKD) occurs in patients with normal NK cell numbers but decreased cytotoxicity. NK cell dysfunction is reported in patients with lymphoma. In turn, lymphoma is the most frequent cancer in patients with PIDD. However, fNKD has not been described in this type of cancer. This work aims to evaluate NK cell phenotype and function in a Chilean cohort of patients with lymphoma.
METHODOLOGY: Blood samples were drawn from twenty-two lymphoma patients and ten healthy donors. A cytotoxicity assay was performed with PBMCs confronted with K562 tumor cells using the LDH release assay. NK cell phenotype was characterized using multiparametric flow cytometry with surface markers for inhibitory and activating ligands, developmental and functional markers.
RESULTS: No significant differences were observed in NK cell counts of lymphoma patients compared to controls (12.28% HD vs 7.48% LYM, p=0.37). No significant differences were observed in the NK cytotoxicity between patients and controls (29.27% HD vs. 16.42% LYM, P=0.33). Interestingly we observed 3 patients with increased cytotoxicity relative to controls and all others with decreased cytotoxic capacity (29.27% HD vs. 11.7% LYM, p=0.011) suggesting that, in terms of NK cell function, two groups of lymphoma patients are identified. NK cell phenotyping revealed significantly lower expression of NKG2C activation marker (21.51 vs. 10.96% LYM, p<0.05) and higher SIGLEC-7 inhibitory marker (54.16vs 81.49, p<0.05) in patients with lymphoma. Other inhibitory, activating and functional NK cell markers showed no significant difference as compared to controls.
CONCLUSION: These results suggest that a subset of patients with lymphoma have NK cell dysfunction despite normal NK cell counts. Genetic determinants of this NK cell dysfunction should be assessed and are part of our future work.