Improved T-cell Immunity Following Neoadjuvant Chemotherapy in Ovarian Cancer.

PURPOSE: Although local tissue-based immune responses are critical for elucidating direct tumor-immune cell interactions, peripheral immune responses are increasingly recognized as occupying an important role in anticancer immunity. We evaluated serial blood samples from patients with advanced epithelial ovarian cancer (EOC) undergoing standard-of-care neoadjuvant carboplatin and paclitaxel chemotherapy (including dexamethasone for prophylaxis of paclitaxel-associated hypersensitivity reactions) to characterize the evolution of the peripheral immune cell function and composition across the course of therapy. EXPERIMENTAL DESIGN: Serial blood samples from 10 patients with advanced high-grade serous ovarian cancer treated with neoadjuvant chemotherapy (NACT) were collected before the initiation of chemotherapy, after the third and sixth cycles, and approximately 2 months after completion of chemotherapy. T-cell function was evaluated using ex vivo IFNγ ELISpot assays, and the dynamics of T-cell repertoire and immune cell composition were assessed using bulk and single-cell RNA sequencing (RNAseq). RESULTS: T cells exhibited an improved response to viral antigens after NACT, which paralleled the decrease in CA125 levels. Single-cell analysis revealed increased numbers of memory T-cell receptor (TCR) clonotypes and increased central memory CD8+ and regulatory T cells throughout chemotherapy. Finally, administration of NACT was associated with increased monocyte frequency and expression of HLA class II and antigen presentation genes; single-cell RNAseq analyses showed that although driven largely by classical monocytes, increased class II gene expression was a feature observed across monocyte subpopulations after chemotherapy. CONCLUSIONS: NACT may alleviate tumor-associated immunosuppression by reducing tumor burden and may enhance antigen processing and presentation. These findings have implications for the successful combinatorial applications of immune checkpoint blockade and therapeutic vaccine approaches in EOC.

Evaluation of ovarian reserve in women with psoriasis.

The aim of this study is to evaluate ovarian reserve in women with psoriasis. Thirty-six women with psoriasis and 36 healthy women were enrolled in this prospective study. On day 3 of the menstrual cycle, blood samples for AMH and other hormones were collected. On the same day, antral follicle count (AFC), and ovarian volumes were measured. A multiple regression analysis was carried out to examine the contribution of factors to the serum AMH levels in patients with psoriasis. The serum AMH levels and ovarian volumes were lower in the psoriasis group than in the control group (1.85 ± 1.13 ng/ml vs 2.46 ± 1.21 ng/ml, p = .029 and 10.43 ± 3.08 cm3 vs 11.93 ± 3.01 cm3, p = .038). However, the mean AFC between the two groups was not significantly different. The psoriasis area severity index (PASI) score did not correlate with AMH. On the other hand, the duration of the disease negatively correlated with AMH, total AFC and ovarian volume. In the multiple regression analysis, duration of disease and total AFC were the most significant contributors to the serum AMH levels in patients with psoriasis. Autoimmune diseases may affect ovarian reserve regardless of immunosuppresive treatment. Longitudinal follow-ups regarding reproductive function might be required in women with psoriasis.