ABSTRACT
Introduction: Natural killer/T cell lymphoma (NKTL) is an aggressive malignancy associated with poor prognosis. This is largely due to limited treatment options, especially for relapsed patients. Immunotherapies like immune checkpoint inhibitors (ICI) and anti-CD38 therapies have shown promising but variable clinical efficacies. Combining these therapies has been suggested to enhance efficacy. Methods: We conducted a case study on a relapsed NKTL patient treated sequentially with anti-CD38 followed by ICI (anti-PD1) using cytometry analyses. Results and Discussion: Our analysis showed an expected depletion of peripheral CD38+ B cells following anti-CD38 treatment. Further analysis indicated that circulating anti-CD38 retained their function for up to 13 weeks post-administration. Anti-PD1 treatment triggered re-activation and upregulation of CD38 on the T cells. Consequently, these anti-PD1-activated T cells were depleted by residual circulating anti-CD38, rendering the ICI treatment ineffective. Finally, a meta-analysis confirmed this counterproductive effect, showing a reduced efficacy in patients undergoing combination therapy. In conclusion, our findings demonstrate that sequential anti-CD38 followed by anti-PD1 therapy leads to a counterproductive outcome in NKTL patients. This suggests that the treatment sequence is antithetic and warrants re-evaluation for optimizing cancer immunotherapy strategies.
Subject(s)
ADP-ribosyl Cyclase 1 , Immune Checkpoint Inhibitors , Humans , ADP-ribosyl Cyclase 1/antagonists & inhibitors , ADP-ribosyl Cyclase 1/metabolism , ADP-ribosyl Cyclase 1/immunology , Immune Checkpoint Inhibitors/therapeutic use , Lymphoma, Extranodal NK-T-Cell/therapy , Lymphoma, Extranodal NK-T-Cell/immunology , Lymphoma, Extranodal NK-T-Cell/drug therapy , Membrane Glycoproteins/antagonists & inhibitors , Male , Programmed Cell Death 1 Receptor/antagonists & inhibitors , Middle Aged , Female , Treatment OutcomeABSTRACT
INTRODUCTION: Studies have suggested that women who present with non-ST-segment elevation myocardial infarction (NSTEMI) may differ in their clinical response to early invasive strategy compared to male patients. We examined the impact of gender difference in NSTEMI patients on outcomes following invasive versus conservative treatment. MATERIALS AND METHODS: Patients enrolled in our national myocardial infarction (MI) registry between January 2000 and September 2005 with diagnosis of NSTEMI were retrospectively analysed. The study endpoint was the occurrence of major adverse cardiac events (MACE) in the patients at 1 year. RESULTS: A total of 1353 patients (62.2% male) with NSTEMI were studied. The mean age of men was 62 +/- 14 versus 72 +/- 12 years in women in the cohort (P <0.001). The prevalence of hypertension and diabetes mellitus were significantly higher in women. Men were more likely to undergo revascularisation than women (OR, 2.97; 95% CI, 2.18-3.89, P <0.001). Among those who were revascularised, there was no gender difference in survival or recurrent MI rates during hospitalisation and at 1 year. Compared to medical therapy, percutaneous coronary intervention (PCI) was associated with a significant reduction in MACE in both women (OR, 0.44; 95% CI, 0.20-0.95) and men (OR, 0.40; 95% CI, 4.79-12.75). The most important predictor of MACE for females was diabetes mellitus (HR, 1.98; 95% CI, 1.17-3.33). CONCLUSIONS: There is a gender-based difference in the rate of revascularisation among patients with NSTEMI. Women benefit from an invasive approach as much as men, despite their advanced age, with similar rates of mortality and recurrent MI at 1-year follow-up.
