(1) IHC revealed that the positive rate of HMGA1 protein was 68.0% (34/50), 53.3% (16/30), and 13. 3% (4/30) in LSCC, atypical hyperplasia of larynx, and laryngeal polyp (p < 0.05), and the positive rate of Ezrin protein was 64.0% (32/50), 50.0% (15/30), and 23.3% (7/30) (p < 0.01), respectively. (2) Real-time PCR demonstrated that the mean relative mRNA expression levels of HMGA1 in LSCC and in normal tissues were 2.41 ± 0.40 and 1.05 ± 0.18, respectively (p < 0.01). The mRNA levels of Ezrin in LSCC and in normal tissues were 1.79 ± 0.27 and 1.04 ± 0.22, respectively (p < 0.05). (3) Western blotting revealed that the mean relative protein expression levels of HMGA1 in LSCC and in normal tissues were 1.73 ± 0.60 and 0.35 ± 0.17, respectively (p < 0.01). The protein levels of Ezrin in LSCC and in normal tissues were 1.82 ± 0.77 and 0.42 ± 0.20, respectively (p < 0.01).
The programmed death (PD) pathway is frequently present in the tumor microenvironment (TME) and suppresses tumor immunity by inhibiting the activity of tumor-infiltrating lymphocytes (TILs), particularly, CD8 + lymphocytes. PD immunotherapy involves stimulation of the immune response in the region surrounding the tumor but is insufficient to prevent tumor progression. Therefore, in this study, we examined the effects of combined PD immunotherapy with fractionated radiotherapy (RT) on antitumor immunity and tumor growth in lymphoma. The immune cell profiles of the TME, blood, and secondary lymphoid organs were determined 7 days after treatment. Four combination therapies were compared. The synergistic effects of αPD-1 mAb and fractionated RT on increased CD8 + lymphocytes in the TME, blood, and secondary lymphoid organs led to substantial tumor regression in mouse EL4 lymphoma, both locally and systemically. Fractionated RT for 4 days followed by αPD-1 mAb therapy was significantly superior to other schemes in terms of overall survival rates and curative rates in xenograft model mice. Our data indicated that substantial immune responses occurred following combination therapy with fractionated RT and αPD-1 mAb immunotherapy. Our findings provide important insights into the use of RT plus αPD-1 mAb as an efficacious combinatorial therapy.
Budesonide can significantly inhibit the proliferation of nasal polyp epithelial cells, down-regulate the expression of GR-alpha mRNA in nasal polyp epithelial cells with time dependence.
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