Cancer stem-like cells (CSCs) have been proposed as a key driving force of tumor growth and relapse in colorectal cancer (CRC), and therefore, they are promising targets for cancer therapy. Epidemiological evidence has suggested that the daily use of aspirin reduces overall mortality of CRC and the risk of distant metastasis. We investigated the effect and mechanism of aspirin on CSCs in CRC.Methods: The ratio of CSCs was analyzed after aspirin treatment both in a cell model and patient samples. Chemically modified aspirin and immunoprecipitation were adopted to detect the target proteins of aspirin. A locus-specific light-inducible epigenetic modification system based on CRISPR technology was constructed to verify the causal relationship in these molecular events. In vivo characterization was performed in a xenograft model.Results: We found that aspirin induces apoptosis in enriched colorectal CSCs, inhibits tumor progression, and enhances the anti-neoplastic effects of chemotherapeutic agents. Furthermore, aspirin directly interacts with p300 in the nucleus, promotes H3K9 acetylation, activates FasL expression, and induces apoptosis in colorectal CSCs. Notably, these effects of aspirin are absent in non-CSCs since H3K9 is hypermethylated in non-CSCs and the effects are not induced by other NSAIDs. In addition, aspirin can suppress oxaliplatin-enriched CSCs and serve as an adjuvant therapy.Conclusions: Taken together, we revealed a unique epigenetic and cox-independent pathway (p300-AcH3K9-FasL axis) by which aspirin eliminates colorectal CSCs. These findings establish an innovative framework of the therapeutic significance of aspirin.

The mechanism responsible for the initiation of tumor metastasis and epithelial-mesenchymal transition (EMT) is not well understood. During EMT, epithelial cells lose their polarity and adhesion to surrounding cells and migrate, resulting in transition into mesenchymal cells. Canonical Wnt signaling has been implicated in controlling gene transcription and body axis pattern formation during development. However, canonical Wnt signaling has also been indicated to serve a role in carcinogenesis by regulating EMT. In the present study, it was demonstrated that the expression of several positive regulators of EMT and Wnt signaling was repressed by aspirin treatment in SW480 tumor cells, and that this reduction was due to alterations in the localization of zinc finger E-box binding homeobox 1 and Snail family transcriptional repressor 2. It was also demonstrated that aspirin may be an effective inhibitor of EMT, reducing the viability and migration ability of SW480 tumor cells, including cells induced by TGF-β1.

In recent years, relying on the human immune system to kill tumour cells has become an effective means of cancer treatment. The development of peptide vaccines, which not only break the immune tolerance of a tumour but also attack malignant cells via specific antitumour immunity, has received increased attention in tumour immunization therapy due to their safety and easy preparation. The use of large‐scale sequencing technology enables the continuous discovery of new tumour antigens. With improved accuracy of epitope prediction by computer simulation and the usage of a tetramer assay, cytotoxic lymphocyte epitopes can be screened and identified more easily. Transmembrane peptide and nanoparticle technologies promote more effective intake and delivery of antigens. Consequently, considerable evolution from universal to personalized peptide vaccines has taken place, and such vaccines induce an efficient and specific immune response targeting tumour neoantigens. Recently, genomic analysis and bioinformatics approaches have greatly facilitated the breakthrough of personalized peptide vaccines targeting neoantigens, resulting in a renewed interest in this field. Further, the combination of tumour peptide vaccines with checkpoint blockades may improve patient outcomes. In this review, we discuss the development of tumour peptide vaccines and the new technological progress, from universalization to personalization, to highlight the substantial promise of tumour peptide vaccines in clinical cancer immunotherapy.

BackgroundSystemic immune dysregulation correlates with cancer progression. However, the clinical implications of systemic immune dysregulation in early non-small cell lung cancer (NSCLC) remain unclear.MethodsUsing a panel of 9 markers to identify 12 parameters in the peripheral blood of 326 patients (34 in the discovery group and 292 in the validation group), we investigated systemic immune dysregulation in early NSCLC. Then, we analyzed the impact of surgery on the systemic immune state of these patients. Finally, we analyzed correlations between systemic immune dysregulation and the clinical features of early NSCLC.ResultsWe found striking systemic immune dysregulation in the peripheral blood of early NSCLC patients. This dysregulation was characterized by a significant decrease in total lymphocytes, T cells, quiescent T cells, CD4+ T cells, and NKT cells. We also observed increased proportions of activated lymphocytes and activated T cells. Systemic immune dysregulation was increased after surgery. Furthermore, systemic immune dysregulation was correlated with multiple clinical features, such as sex, age, smoking history, pathological type, tumor stage, surgical approach, tumor differentiation, and epidermal growth factor receptor (EGFR) mutation. Finally, we observed that systemic immune dysregulation was correlated with complications and systemic inflammatory response syndrome (SIRS) in early NSCLC patients.ConclusionsOur results reveal systemic immune dysregulation occurring in early NSCLC and demonstrate the correlation between these dysregulations and clinical features. Our findings suggest that systemic immune dysregulation is involved in cancer development and may be a promising candidate for high-risk screening and treatment strategies for early NSCLC.

Our data suggested that hnRNPC1/2 upregulates p27(kip1) expression and the subsequent suppression of cell proliferation and induction of apoptosis, thereby providing an important mechanism whereby gastric epithelial cells antagonize CagA-mediated pathogenesis.