Polyphenols and their derivates, a kind of natural product distributed in herb plants, vegetables, and fruits, are the most abundant antioxidants in the human diet and have been found to display cancer-preventative effects in several epidemiological studies. The scientific community has also validated the anti-cancer bioactivities and low toxicities of polyphenolic compounds, including flavones, tannins, phenolic acids, and anthocyanins, through in vitro and in vivo studies. However, the low stability, weak targeting ability, poor solubility, and low bioavailability of pure polyphenolic agents have significantly impaired their treatment efficacy. Nowadays, nano-based technology has been applied to surmount these restrictions and maximize the treatment efficacy of polyphenols. In this review, we summarize the advantages and related mechanisms of polyphenols in cancer treatment. Moreover, aiming at the poor solubility and low bioavailability of pure polyphenols in vivo, the advantages of nano-based delivery systems and recent research developments are highlighted. Herein, particular emphasis is mainly placed on the most widely used nanomaterials in the delivery of natural products, including liposomes, micelles, and nanogels. Finally, we present an overview and the challenges of future implementations of nano-based delivery systems of polyphenolic compounds in the cancer therapeutic field.

Objectives: Although adoptive cell therapy with T‐cell receptor‐engineered T cells (TCR‐Ts) has mediated effective antitumor responses in several cancers, senescence of T cells could impair the therapeutic effect of TCR‐Ts. Thus, it is essential to elucidate the characteristics of senescent TCR‐Ts and how to subsequently improve their antitumor effect. Here, we focused on the influence of autophagy on TCR‐Ts, since autophagy is tightly associated with the regulation of T‐cell activation, proliferation and differentiation.Methods: We first evaluated autophagy level of senescent TCR‐Ts, and then the senescent TCR‐Ts were expanded in vitro for 7 days with and without spermidine treatment, respectively. Furthermore, the proliferative potential, phenotypical characteristics and functionality of the propagated senescent TCR‐Ts were analysed in vitro and in vivo after 7‐day ex vivo expansion.Results: We found that autophagic flux of senescent TCR‐T cells was significantly impaired. The restoration of autophagic flux via spermidine treatment reduced the expression of inhibitory immunoreceptors (PD‐1, TIM‐3 or LAG‐3), enhanced proliferation and effector functions and subsequently demonstrated the superior in vitro and in vivo antitumor activity of TCR‐Ts.Conclusion: These data suggest that spermidine treatment presents an opportunity to improve the antitumor effect of TCR‐Ts for the treatment of solid tumors.

Background: Thoracic adenoid cystic carcinoma (ACC) is rare, and the differences between tracheal and lung lesions have not been fully understood.Methods: Patients were identified from a Chinese cancer center (FUSCC) (2005–2022) and the Surveillance, Epidemiology, and End Results (SEER) database (2000–2019). Incidence was calculated and trends were quantified. Clinicopathological features and overall survival (OS) were analyzed. Nomograms predicting OS were constructed.Results: Totally, 55 tracheal adenoid cystic carcinoma (TACC) and 25 lung and bronchus adenoid cystic carcinoma (LACC) were included in a Chinese cohort, 121 TACC and 162 LACC included in the SEER cohort. There were larger tumor sizes, more lymph nodes and distant metastases for LACC than TACC patients. TACC patients are more likely to get local treatments. Patients with LACC had significantly worse median OS than patients with TACC (SEER cohort: 68.0 months vs. 109.0 months, p = 0.001, Chinese cohort: 62.9 months vs. 124.8 months, p = 0.061). Age, lymph node metastasis, distant metastasis and local treatment were identified as independent prognostic factors for OS of TACC. Distant metastasis and local treatment were identified for LACC. Specifically, surgery alone or in combination with radiotherapy is crucial for improving survival in both TACC and LACC. Only TACC benefits from radiotherapy alone, while chemotherapy does not improve survival for either. The nomograms constructed using these factors revealed good prognostic accuracy.Conclusions: LACC is more aggressive and has a worse prognosis than TACC. TACC patients have more opportunities for local treatment, which is important for the prognosis of both TACC and LACC. Nomograms were created for TACC and LACC to aid in personalized survival predictions and clinical decisions.

Merkel cell carcinoma (MCC) is a primary cutaneous neoplasm of neuroendocrine carcinoma of the skin, which is characterized by molecular heterogeneity with diverse tumour microenvironment (TME). However, we are still lack knowledge of the cellular states and ecosystems in MCC. Here, we systematically identified and characterized the landscape of cellular states and ecotypes in MCC based on a machine learning framework. We obtained 30 distinct cellular states from 9 immune cell types and investigated the B cell, CD8 T cell, fibroblast, and monocytes/macrophage cellular states in detail. The functional profiling of cellular states were investigated and found the genes highly expressed in cellular states were significantly enriched in immune- and cancer hallmark-related pathways. In addition, four ecotypes were further identified which were with different patient compositions. Transcriptional regulation analysis revealed the critical transcription factors (i.e. E2F1, E2F3 and E2F7), which play important roles in regulating the TME of MCC. In summary, the findings of this study may provide rich knowledge to understand the intrinsic subtypes of MCCs and the pathways involved in distinct subtype oncogenesis, and will further advance the knowledge in developing a specific therapeutic strategy for these MCC subtypes.