sublingual immunotherapy

Cancer Immunotherapy and Immune-Related Adverse Events: Focusing on Non-Small Cell Lung Cancer.

Kamil Atif A, Cowles Sara S, Driver Casaundra C CC, Arora Aakriti A et al.

The development of immunotherapy has changed the paradigm of cancer treatment. In particular, immune checkpoint inhibitors (ICIs) demonstrate therapeutic efficacy and improve patient survival across multiple cancer types. Currently, however, only a subset of cancer patients can achieve objective therapeutic responses and gain survival benefits from immunotherapy. Treatment-associated side effects, namely immune-related adverse events (irAEs), may cause autoimmune and inflammatory complications in various organ systems and hinder the use of immunotherapy in cancer patients. Herein, the development of cancer immunotherapy and the modulatory roles of the tumor immune microenvironment, with a focus on ICI therapy in non-small cell lung cancer (NSCLC), are reviewed. The grading, types, biomarkers, and treatment of irAEs are also discussed. More research is needed to further increase the efficacy of cancer immunotherapy and alleviate irAEs.

Giant Bilateral Submandibular Dermoid Cysts.

Zhai Yuxiang Y, Huang Jiale J, Chen Renji R, Song Qinggao Q

Dermoid cysts are benign developmental lesions arising from ectodermal remnants formed during embryogenesis, predominantly observed in children and young adults. These cysts most frequently occur in the floor of the mouth and submental region, typically located deep within the mucosa or subcutaneous tissue, or between the muscles of the floor of the mouth. Herein, we present a case of a 39-year-old male with a 30-year history of bilateral submandibular masses. Magnetic resonance imaging revealed a sublingual cystic lesion extending into the bilateral submandibular spaces, with well-demarcated borders. After exclusion of contraindications for general anesthesia, complete resection of the lesion was performed. Postoperative histopathologic examination confirmed an epidermoid cyst. The patient achieved a favorable postoperative outcome without signs of recurrence.

Adjuvant immunotherapy survival: Aligning eligibility, treatment assignment and time zero.

Jiang Fangrong F, Shen Ting T

In Vivo CRISPR Screen Identifies RPS19 as an Immunotherapy Target in Hepatocellular Carcinoma.

He Lei L, Yu Duo D, Xie Fei F, Hou Kaisheng K et al.

Despite the remarkable clinical success of immunotherapy, its efficacy against hepatocellular carcinoma (HCC) remains severely limited, highlighting an urgent need for novel targets and strategies to overcome immune evasion. Here, we aimed to identify key regulators of HCC immunity via unbiased functional screening and develop a targeted therapy to remodel the immunosuppressive tumor microenvironment (TME). We performed an in vivo CRISPR-knockout screen using a 4500-gene sgRNA library in syngeneic HCC mouse models. Single-cell RNA sequencing of human HCC tissues and in vivo macrophage-depletion assays were utilized to dissect cellular populations and validate underlying mechanisms. We identified ribosomal protein S19 (RPS19) as a central mediator of HCC immune evasion, whose deletion in HCC cells mitigates the immunosuppressive TME. Mechanistically, scRNA-seq pinpointed tumor-associated macrophages as the key effector subset, whereby complement C5a receptor 1 (C5aR1) transduces RPS19 signals to trigger macrophage-dependent immune suppression. We further constructed SP94-peptide-modified disulfide-bond-containing nanoparticles (SNPSS) for targeted CRISPR-Cas9 delivery. SNPSS efficiently homes to HCC cells, releases payloads within the glutathione-rich TME, downregulates RPS19, reverses immune suppression, and robustly suppresses HCC progression in vivo. Collectively, the RPS19-C5aR1-macrophage axis fuels HCC immune escape, and SNPSS-based RPS19 gene-editing offers a promising strategy to remodel the TME and boost HCC immunotherapy efficacy.