In this study, the etiology, clinical characteristics, and prognosis of multiple primary malignant tumors (MPMTs) were investigated. Furthermore, we analyzed the treatment factors associated with MPMTs. From 15,398 patients with malignant tumors presenting to The First Hospital of Jilin University, China, between January 2010 and December 2013, we identified and analyzed patients with MPMTs. Data were obtained retrospectively from the hospital database. The prevalence of MPMTs in this study was 0.99% (152/15398): 51 cases were synchronous MPMTs, and 101 cases were metachronous MPMTs. The mean time between the first and second primary cancer was 43.1 months. In this population, MPMTs were observed more frequently in patients with head and neck tumors (5.65%) and urinary tumors (4.19%); the prevalence of MPMTs in these patients was over 4-fold greater than the prevalence of MPMTs in all patients (0.99%). There were no cases of MPMTs in 132 cases of nervous system tumors and 404 cases of multiple myeloma. Nearly 50% (45.4%) of patients with MPMTs did not receive chemotherapy or radiotherapy before the second primary cancer was diagnosed. Eighty-five patients with MPMTs were followed for more than 2 years, and the 2-year cumulative survival rate was 40.8%. In this study, the prevalence of MPMTs was 0.99% (152/15398), which is consistent with the Chinese literature. Patients with head and neck tumors or urinary tumors are at greater risk of developing MPMTs. In addition to radiotherapy or chemotherapy, this study suggests that other factors may contribute to MPMTs.

Tumor cell apoptosis induced by radiation therapy results in apoptotic tumor cells and apparition of membrane blebs termed apoptotic bodies (APB). The immune responses induced by apoptotic tumor cells have been extensively studied. However, the role of APB in modulation of tumor immune responses is elusive. In this study, we induced apoptosis in 90% ovabumin-expressing EG7 tumor cells by in vitro irradiation (9,000 rad) of tumor cells with a subsequent cell culture for 9 hours. APB purified from irradiation-induced apoptotic EG7 cell culture supernatant by differential ultracentrifugation were vesicles with 50 to 90 nm in diameter and expressed apoptosis-specific Annexin V, 14-3-3, and Histone H3. We then investigated its potential modulation in DC_OVA–induced T-cell responses and antitumor immunity. We found that EG7-derived APB were tolerogenic and capable of suppressing DC_OVA-stimulated CD8⁺ CTL responses and antitumor immunity via its induction of CD8⁺ T-cell anergy and type 1 regulatory CD4⁺ T-cell responses. Analysis of apoptotic tumor cells and APB revealed the expression of membrane-bound transforming growth factor (TGF)-β1 associated with irradiation-induced apoptosis formation, which is a result from activation of transcriptional factor NF-AT specific for TGF-β1 promoters. Our data further elucidate that it is the membrane-bound TGF-β1 expression on APB that contributes to its in vitro antiproliferative effect as shown by using neutralizing TGF-β1–specific antibody. Administration of anti–TGF-β1 antibody in vivo also blocked APB-mediated immune suppression of CD8⁺ CTL responses and antitumor immunity. Therefore, our study may have great impact in designing a combined radiation therapy with immunotherapy of cancer. [Cancer Res 2009;69(19):7756–66]

Histone deacetylases (HDACs) are a class of epigenetic regulators that play pivotal roles in key biological processes such as cell proliferation, differentiation, metabolism, and immune regulation. Based on this, HDAC inhibitors (HDACis), as novel epigenetic-targeted therapeutic agents, have demonstrated significant antitumor potential by inducing cell cycle arrest, activating apoptosis, and modulating the immune microenvironment. Current research is focused on developing highly selective HDAC isoform inhibitors and combination therapy strategies tailored to molecular subtypes, aiming to overcome off-target effects and resistance issues associated with traditional broad-spectrum inhibitors. This review systematically elaborates on the multidimensional regulatory networks of HDACs in tumor malignancy and assesses the clinical translation progress of next-generation HDACis and their prospects in precision medicine, providing a theoretical framework and strategic reference for the development of epigenetic-targeted antitumor drugs.