Background: Ovarian cancer typically presents at an advanced stage, and although the majority of cases initially respond well to platinum-based therapies, chemoresistance always occurs leading to a poor long-term prognosis. Multiple resistance mechanisms have already been identified including the tumor microenvironment (TME). The immune cells within the TME often play an important role in tumor occurrence and development. However, whether there are differences between different platinum-responsive ovarian cancer patients in the number and functions of immune cells in the TME as well as the possible mechanisms affecting the drug efficiency of tumor cells remains unknown. Methods: To comprehensively characterize the ovarian cancer immune system, we used single-cell RNA sequencing to profile 61345 cells from 3 platinum-resistant and 6 platinum-sensitive patients. We found that the number of NK cell subpopulations are the most significantly distinct immune cells among platinum-resistant and platinum-sensitive patients. Then we performed immunohistochemistry to verify this difference in paraffin section of ovarian cancer patients. Moreover, we co-cultured ovarian cancer cell lines with different NK cell subpopulations and tested the drug responsiveness of the former, in order to comparing the effects of NK cell subpopulations on tumor cells platinum-based drug responsiveness. Results: Our single-cell sequencing results found that platinum-resistant ovarian cancer patients compared with platinum-sensitive patients has a decreased proportion of CD16+ NK cells and an increased proportion of CD16-NK cells in the tumor microenvironment. Besides, compared with platinum-sensitive patients, there is an increase in the expression of inhibitory genes and a decrease in the expression of activating genes of NK cells in platinum-resistant ovarian cancer patients. Histological section showing that platinum-resistant ovarian cancer patients versus platinum-sensitive patients has fewer NK cells in the TME and decreased CD16 expression on the surface of NK cells. Cytotoxicity assay reveals that ovarian cancer cell lines co-cultured with CD16+NK cells show better responsiveness to platinum than that co-cultured with CD16-NK cells. Conclusions: Our results demonstrate that the NK cells activity is worse in platinum-resistant ovarian cancer patients and CD16-NK plays a role in weakening the drug responsiveness of ovarian malignant tumor cells.
CLO25-070: FIGURE.
Citation: Journal of the National Comprehensive Cancer Network 23, 3.5; 10.6004/jnccn.2024.7153
