Engineered nanomedicines block the PD-1/PD-L1 axis for potentiated cancer immunotherapy.

Immunotherapy, in particular immune checkpoint blockade (ICB) therapy targeting the programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1) axis, has remarkably revolutionized cancer treatment in the clinic. Anti-PD-1/PD-L1 therapy is designed to restore the antitumor response of cytotoxic T cells (CTLs) by blocking the interaction between PD-L1 on tumour cells and PD-1 on CTLs. Nevertheless, current anti-PD-1/PD-L1 therapy suffers from poor therapeutic outcomes in a large variety of solid tumours due to insufficient tumour specificity, severe cytotoxic effects, and the occurrence of immune resistance. In recent years, nanosized drug delivery systems (NDDSs), endowed with highly efficient tumour targeting and versatility for combination therapy, have paved a new avenue for cancer immunotherapy. In this review article, we summarized the recent advances in NDDSs for anti-PD-1/PD-L1 therapy. We then discussed the challenges and further provided perspectives to promote the clinical application of NDDS-based anti-PD-1/PD-L1 therapy.

Multidisciplinary team therapy for left giant adrenocortical carcinoma: A case report.

BACKGROUND: Adrenocortical carcinoma (ACC) is a rare malignant epithelial tumor originating from adrenocortical cells that carries a very poor prognosis. Metastatic or inoperable diseases are often considered incurable, and treatment remains a challenge. Especially for advanced cases such as ACC complicated with renal venous cancer thrombus, there are few cumulative cases in the literature. CASE SUMMARY: The patient in this case was a 39-year-old middle-aged male who was admitted to the hospital for more than half a month due to dizziness and chest tightness. Computed tomography (CT) findings after admission revealed a left retroperitoneal malignant space-occupying lesion, but the origin of the formation of the left renal vein cancer thrombus remained to be determined. It was speculated that it originated from the left adrenal gland, perhaps a retroperitoneal source, and left adrenal mass + left nephrectomy + left renal vein tumor thrombus removal + angioplasty were performed under general anesthesia. Postoperative pathology results indicated a diagnosis of ACC. Postoperative steroid therapy was administered. At 3 mo after surgery, abdominal CT reexamination revealed multiple enlarged retroperitoneal lymph nodes and multiple low-density shadows in the liver, and palliative radiotherapy and mitotane were administered, considering the possibility of metastasis. The patient is currently being followed up. CONCLUSION: ACC is a highly malignant tumor. Even if the tumor is removed surgically, there is still the possibility of recurrence. Postoperative mitotane and adjuvant chemoradiotherapy have certain benefits for patients, but they cannot fully offset the poor prognosis of this disease.

[Recombinant adenovirus-mediated RNA silencing of tissue factor expression in human islet: an in vitro study].

OBJECTIVE: To construct a replication-incompetent recombinant adenovirus mediating short hairpin RNA (shRNA)-induced tissue factor gene silencing in the islet. METHODS: Four pairs of complementary oligonucleotides were designed and synthesized to create double-stranded oligonucleotides (ds oligo). The ds oligos were cloned into Pentr/U6 vector to construct the shuttle plasmid pENTR/U6-shRNA, which was transduced into human islets via liposome after sequence verification. The plasmid with the best silencing effect was identified by real-time RT-PCR, followed by homologous recombination with the adenovirus backbone plasmid. The functional clone was transfected into 293A cells to amplify the adenovirus, whose silencing effect against TF expression was tested using real-time RT-PCR and Western blotting. RESULTS: The pENTR/U6-shRNA shuttle plasmid was constructed and verified by sequencing. The recombinant adenovirus-mediated shRNA against TF was constructed, and real-time RT-PCR and Western blotting demonstrated that the strongest silencing effect of the adenovirus against TF occurred on the 4th day following islet transfection. CONCLUSION: Replication-incompetent recombinant adenovirus-mediated shRNA against TF has been successfully constructed, which has good silencing effect against TF expression in human islet in vitro.