Abstract
Primary pulmonary nuclear protein of testis carcinoma is a rare and highly aggressive malignant tumor. It accounts for approximately 0.22% of primary thoracic tumors and is little known, so it is often misdiagnosed as pulmonary squamous cell carcinoma. No effective treatment has been formed yet, and the prognosis is extremely poor. This review aims to summarize the etiology, pathogenesis, diagnosis, treatment, and prognosis of primary pulmonary nuclear protein of testis carcinoma in order to better recognize it and discuss the current and innovative strategies to overcome it. With the increasing importance of cancer immunotherapy and tumor microenvironment, the review also discusses whether immunotherapy and targeting the tumor microenvironment can improve the prognosis of primary pulmonary nuclear protein of testis carcinoma and possible treatment strategies. We reviewed and summarized the clinicopathological features of all patients with primary pulmonary nuclear protein of testis carcinoma who received immunotherapy, including initial misdiagnosis, disease stage, immunohistochemical markers related to tumor neovascularization, and biomarkers related to immunotherapy, such as PD-L1 (programmed death-ligand 1) and TMB (tumor mutational burden). In the meanwhile, we summarized and analyzed the progression-free survival (PFS) and the overall survival (OS) of patients with primary pulmonary nuclear protein of testis carcinoma treated with PD-1 (programmed cell death protein 1)/PD-L1 inhibitors and explored potential population that may benefit from immunotherapy. To the best of our knowledge, this is the first review on the exploration of the tumor microenvironment and immunotherapy effectiveness in primary pulmonary nuclear protein of testis carcinoma.
Highlights
The nuclear protein of testis (NUT) carcinoma is defined by the NUT gene rearrangement
We consider that anti-VEGF therapy combined with PD-1/PD-L1 inhibitor plus chemotherapy may be beneficial to patients with primary pulmonary NUT carcinoma
It has been confirmed that tumor-derived IL-8 can promote tumor angiogenesis, recruit myeloid derived suppressor cells (MDSCs) to suppress anti-tumor immune responses (Figure 5) and maintain the epithelial mesenchymal transition phenotype of tumor cells, thereby participating in the proliferation and metastasis of tumor cells [107,108,109,110]
Summary
The nuclear protein of testis (NUT) carcinoma is defined by the NUT ( known as NUTM1) gene rearrangement. The median age of NUT carcinoma patients is 23.6 years old (range=18days-80years) and is 30 years old (range=21years-68years) for primary pulmonary NUT carcinoma, respectively [6, 15]. It binds BRD4-NUT fusion oncoprotein to histone acetylated lysine residues in chromatin via two bromodomains. The NUT protein can recruit the histone acetyltransferase (HAT) p300 It acetylates adjacent histones, which in turn allows more BRD4NUT fusion oncoproteins to bind to chromatin and recruit transcription factors, such as positive transcription elongation factor b (P-TEFb) [25, 26]. BRD4-NUT fusion oncoprotein sequesters histone acetyltransferases (HATs) and other transcriptional co-factors to the chromatin regions that transcribe pro-proliferative and anti-differentiation genes, such as MYC, TP63, SOX2 [27,28,29]. The complex causes local chromatin lahyperacetylation, which promotes tumor growth and inhibition differentiation [8, 35]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
