br Conflict of Interest br Acknowledgments The

Conflict of Interest
Acknowledgments The authors acknowledge grant from Department of Atomic Energy (DAE), Govt. of India, Grant number: 2013/35/45/BRNS and the technical support of the MSSB (Molecular Stress and Stem Cell Biology) group, School of Biotechnology. We would also like to thank Dr. Surajit Bhattacharjee, Assistant Professor, Department of Molecular Biology & Bioinformatics, Tripura University for his care for reading the manuscript.
Pituitary adenoma is a common intracranial tumor that accounts for 10%–20% of all primary intracranial tumors, and its incidence rate is second only to glioma and meningioma. Moreover, according to epidemiologic investigations, the morbidity of pituitary adenoma increases annually. The occurrence and development of tumors are complex processes that involve many aspects, such as immune status, cell differentiation, and apoptosis. Therefore, exploring the relevant molecular mechanisms that contribute to the clinical diagnosis and treatment of pituitary adenoma is important. Natural killer (NK) PHA-793887 and T lymphocytes can activate cytotoxicity by binding to the major histocompatibility complex (MHC) class I chain-related molecule A (MICA) ligands on the surface of tumor cells, killing tumor cells. However, there are multiple immune escape mechanisms in various tumor cells, primarily by avoiding recognition by cytotoxic cells, directly impairing the functioning of antigen-presenting cells or cytotoxic cells, or inducing suppressor cells. It is known that tumor cells secrete a soluble MHC class I chain-related molecule A (sMICA) that can bind to natural killer group 2d (NKG2D) and downregulate its expression to promote immune escape., Matrix metalloproteinase (MMP), a type of zinc-dependent enzyme, plays an important role in the degradation of extracellular matrix in the tumor microenvironment. In osteosarcoma, matrix metalloproteinase 9 (MMP-9) promotes the release of sMICA from tumor cells, and MMP-9 inhibitors increase the expression of membrane-anchored MHC class I chain-related molecule A (mMICA) and decrease sMICA release without inhibiting MICA mRNA transcription. Therefore, MMP-9 plays an important role in sMICA-mediated tumor immune escape. p38/mitogen-activated protein kinase (p38/MAPK) is a major pathway among the MAPK signal transduction pathways. Activation of the p38/MAPK pathway activates downstream nuclear transcription factors and regulates the expression of related genes, which affect cellular responses such as cell proliferation, differentiation, inflammation, and apoptosis. Recent studies have indicated that the p38/MAPK pathway significantly involves in tumor invasion and metastasis formation in various cell lines by regulating the expression of MMPs family. The p38/MAPK pathway regulates the expression of MICA by activating the E2F transcription factor 1. This study detects the expression levels of phospho-p38, MMP-9, and MICA proteins and evaluates the relationships between them in pituitary adenomas to provide a histologic basis for mechanistic research on the function of the NKG2D-MICA pathway in pituitary adenoma immune escape. Materials and Methods
Results
Discussion Pituitary adenoma is a common epithelial cell–derived tumor. The treatment strategies for pituitary adenoma primarily include radiotherapy, drug treatment, and surgery, which is the preferred treatment. However, pituitary adenoma is still prone to recurrence and is poorly controlled, so discovering new treatment strategies is urgent. Infiltration of immune cells in pituitary adenoma suggest increased probability for immunotherapy based on the memory characteristic of immune cells and the specificity of immunotherapy, which may inhibit tumor recurrence. With advances in research regarding the immunotherapy of pituitary adenoma, immunotherapy is expected to become another important treatment for pituitary adenoma.