Myo1e overexpression in lung adenocarcinoma is associated with increased risk of mortality.

This study aims to perform a comprehensive genomic analysis to assess the influence of overexpression of MYO1E in non-small cell lung carcinoma (NSCLC) and whether there are differences in survival and mortality risk in NSCLC patients depending on both DNA methylation and RNA expression of MYO1E. The DNA methylation probe cg13887966 was inversely correlated with MYO1E RNA expression in both LUAD and LUSC subpopulations showing that lower MYO1E RNA expression was associated with higher MYO1E DNA methylation. Late stages of lung cancer showed significantly lower MYO1E DNA methylation and significantly higher MYO1E RNA expression for LUAD but not for LUSC. Low DNA methylation as well as high RNA expression of MYO1E are associated with a shorter median survival time and an increased risk of mortality for LUAD, but not for LUSC. This study suggests that changes in MYO1E methylation and expression in LUAD patients may have an essential role in lung cancer's pathogenesis. It shows the utility of MYO1E DNA methylation and RNA expression in predicting survival for LUAD patients. Also, given the low normal expression of MYO1E in blood cells MYO1E DNA methylation has the potential to be used as circulating tumor marker in liquid biopsies.

Evaluation of a ConvitVax/anti-PD-1 combined immunotherapy for breast cancer treatment.

Breast cancer therapies using checkpoints alone have not been highly effective. Based on previous experiences using the ConvitVax, an autologous tumor cells/bacillus Calmette-Guérin (BCG)/formalin-based vaccine, in breast cancer and the potential success of combined therapies, we sought to ascertain whether the ConvitVax combined with anti-PD-1 enhances the antitumor effect in a 4T1 breast cancer model. Animals received four weekly injections of either PBS (G1), ConvitVax (200 µg cell homogenate, 0.0625 mg BCG, 0.02% formalin) (G2), 50 µg anti-PD-1 (G3), or ConvitVax plus anti-PD-1 (200 µg cell homogenate, 0.0625 mg BCG, 0.02% formalin, 50 µg anti-PD-1) (G4). Five weeks post tumor induction all mice were euthanized, tumors extracted and evaluated pathologically and by immunohistochemistry. The combination group (G4) showed 10% more tumor necrosis, greater infiltration of PD-1+ cells and lower infiltration of TAMs, evidencing that the combination of ConvitVax and anti-PD-1 can improve the antitumor effect of the vaccine. Using a higher anti-PD-1 dose and administering each treatment at different times could further potentiate the effect of our therapy. Given the vaccine's low cost and simple preparation, its use in combination with checkpoints or other target-specific compounds may lead to a highly effective personalized breast cancer immunotherapy.

Autologous tumor cells/bacillus Calmette-Guérin/formalin-based novel breast cancer vaccine induces an immune antitumor response.

Autologous cancer cell vaccines represent a multivalent patient-specific treatment. Studies have demonstrated that these immunotherapies should be combined with immunomodulators to improve results. We tested in breast cancer the antitumor effects of a 200 µg autologous tumor cells homogenate combined with 0.0625 mg of bacillus Calmette-Guérin (BCG), and 0.02% formalin. We used a 4T1 murine model of BALB/c receiving four weekly injections of either this vaccine or control treatments. The control treatments were either Phosphate Buffer Saline, BCG treated with formalin, or the tumor cells homogenate plus BCG alone. We found that mice treated with the vaccine had the lowest tumor growth rate and mitosis percentage. The vaccinated group also showed a marked increase in infiltration of antitumor cells (natural killer, CD8 + T and CD4+ Th1 cells), as well as a decrease of myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs). Additionally, we also observed a possible activation of the immune memory response as indicated by plasma cell tumor infiltration. Our results demonstrate that our proposed breast cancer vaccine induces a potent antitumor effect in 4T1 tumor-bearing mice. Its effectiveness, low cost and simple preparation method, makes it a promising treatment candidate for personalized breast cancer immunotherapy.