Gold nanoparticle-directed autophagy intervention for antitumor immunotherapy via inhibiting tumor-associated macrophage M2 polarization

Tumor-associated macrophages (TAMs), one of the dominating constituents of tumor microenvironment, are important contributors to cancer progression and treatment resistance. Therefore, regulation of TAMs polarization from M2 phenotype towards M1 phenotype has emerged as a new strategy for tumor immunotherapy. Herein, we successfully initiated antitumor immunotherapy by inhibiting TAMs M2 polarization via autophagy intervention with polyethylene glycol-conjugated gold nanoparticles (PEG-AuNPs). PEG-AuNPs suppressed TAMs M2 polarization in both in vitro and in vivo models, elicited antitumor immunotherapy and inhibited subcutaneous tumor growth in mice. As demonstrated by the mRFP-GFP-LC3 assay and analyzing the autophagy-related proteins (LC3, beclin1 and P62), PEG-AuNPs induced autophagic flux inhibition in TAMs, which is attributed to the PEG-AuNPs induced lysosome alkalization and membrane permeabilization. Besides, TAMs were prone to polarize towards M2 phenotype following autophagy activation, whereas inhibition of autophagic flux could reduce the M2 polarization of TAMs. Our results revealed a mechanism underlying PEG-AuNPs induced antitumor immunotherapy, where PEG-AuNPs reduce TAMs M2 polarization via induction of lysosome dysfunction and autophagic flux inhibition. This study elucidated the biological effects of nanomaterials on TAMs polarization and provided insight into harnessing the intrinsic immunomodulation capacity of nanomaterials for effective cancer treatment.

Current status of clinical researches on metastatic triple negative breast cancer / 国际肿瘤学杂志

Triple negative breast cancer (TNBC) is associated with a high risk of recurrence and generally a poor prognosis. Median survival time of metastatic triple negative breast cancer (mTNBC) is about one year. Currently, the mainstay of treatment for mTNBC remains cytotoxic chemotherapy. In recent years, the drugs involved in the clinical researches of mTNBC include poly-ADP-ribose polymerase inhibitors, phosphoinositide 3-kinase pathway inhibitors, antibody targeting epidermal growth factor receptor, antibody targeting trophoblast surface antigen-2, antibody targeting death receptor 5, endocrine therapy drugs for androgen receptor, and immune checkpoint inhibitors and so on. New drugs have gradually improved the survival of patients with mTNBC.

Advances in diagnosis and treatment of small bowel adenocarcinoma / 中国肿瘤临床

Small bowel adenocarcinoma (SBA) is a relatively uncommon neoplasm with poor prognosis. However, the incidence rate of this condition increases. SBA is usually diagnosed at the late stages, and the majority of patients present with the advanced stage. Data are limited when making decisions for treatment because of the lack of randomized trials for SBA. Radical surgery is considered necessary when possible. Adjuvant chemotherapy is predicted to be beneficial, but this procedure has not yet been investigated through randomized trials. Platinum-based chemotherapy is apparently the most effective treatment regimen used in retrospective tri-als for advanced SBA. Targeted therapies, such as those against the angiogenetic pathway or the epidermal growth factor receptor pathway, have not yet been established for this type of cancer. This article reviews the progress in the diagnosis and treatment of SBA.