Designing of CD8 T cell vaccines which would provide protection against tumors is still considered a great challenge in immunotherapy. Here we show a robust potential of a cytomegalovirus (CMV) vector expressing the NKG2D ligand RAE-1γ as CD8 T cell-based vaccine against malignant tumors. Immunization with the CMV vector expressing RAE-1γ delayed tumor growth or even provided complete protection against tumor challenge in both prophylactic and therapeutic settings. Moreover, a potent tumor control in mice vaccinated with this vector can be further enhanced by blocking the immune checkpoints TIGIT and PD-1. Expression of RAE-1γ by the CMV vector potentiated expansion of KLRG1+ CD8 T cells with enhanced effector properties. This vaccination was even more efficient in neonatal mice, resulting in the expansion and long-term maintenance of epitope-specific CD8 T cells conferring robust resistance against tumor challenge. Our data show that immunomodulation of CD8 T cell responses promoted by herpesvirus expressing a ligand for NKG2D receptor can provide a powerful platform for the prevention and treatment of CD8 T cell-sensitive tumors.
Purpose Lower urinary tract symptoms (LUTS) can have an etiology outside the lower urinary tract (LUT) and are therefore an important diagnostic indicator for assessing the overall health of a person. However, LUTS is still mainly neglected by primary health care providers as well as by patients. In this study, we assessed the importance of an educational interview (EI) conducted by a GP on the patients’ ability to recognize LUTS. We also investigated other factors that affect the recognition of LUTS: subjects’ personal educational level, number of LUT symptoms and their bothersome level on a scale 0–10. Patients and Methods This cross-sectional study was conducted in Croatia (2018–2020) by interviewing 499 subjects. We compared recognized LUT symptoms before and after the EI and determined whether their number, their bothersome level, or the subjects’ personal educational level were associated with LUTS recognition. Results EI significantly improved the ability to recognize LUTS (p=0.001). The number of LUT symptoms and bothersome level in subjects before EI was much greater than the number in subjects after EI (p<0.0001, mean>4 and p<0.0001, median>8, respectively). Subjects with higher educational level recognized LUTS with fewer symptoms after the EI (p<0.01), but no difference was observed among subjects who recognized LUTS before the EI. Conclusion For subjects to recognize LUTS, their condition had to be severe – more than 4 symptoms and bothersome level >8/10. Personal educational level had little impact on LUTS recognition. However, an EI proved to be an excellent tool for raising awareness about LUTS and its early recognition.
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