Aggregation-Induced Emission-Based Vaccine Improves Potential Antitumor Immunotherapy

Recently, immunomodulation based on biomaterials has held great promise for preventing and treating cancer. Tumor vaccination can be considered as one of promising immunotherapies, compared with the vaccines for infectious disease, it still stays in its infant. Herein, we designed a near-infrared-emitting AIEgens (named TPE-Ph-DCM) based vaccine as an adjuvant in enhancing immune response. AIE-based photodynamic vaccine exhibited efficiently enhancement of the DC?s antigen prestation and elicited antigen-specific cytotoxic T lymphocyte functionality, and significantly inhibited B16-OVA tumor growth prophylactically and therapeutically in mice model. This study is expected to provide a scientific basis for developing effective and safe tumor vaccines.

Identification of immune-related subtypes of colorectal cancer to improve antitumor immunotherapy

Immunotherapy involving immune checkpoint inhibitors (ICIs) for enhancing immune system activation is promising for tumor management. However, the patients’ responses to ICIs are different. Here, we applied a non-negative matrix factorization algorithm to establish a robust immune molecular classification system for colorectal cancer (CRC). We obtained data of 1503 CRC patients (training cohort: 488 from The Cancer Genome Atlas; validation cohort: 1015 from the Gene Expression Omnibus). In the training cohort, 42.8% of patients who exhibited significantly higher immunocyte infiltration and enrichment of immune response-associated signatures were subdivided into immune classes. Within the immune class, 53.1% of patients were associated with a worse overall prognosis and belonged to the immune-suppressed subclass, characterized by the activation of stroma-related signatures, genes, immune-suppressive cells, and signaling. The remaining immune class patients belonged to the immune-activated subclass, which was associated with a better prognosis and response to anti-PD-1 therapy. Immune-related subtypes were associated with different copy number alterations, tumor-infiltrating lymphocyte enrichment, PD-1/PD-L1 expression, mutation landscape, and cancer stemness. These results were validated in patients with microsatellite instable CRC. We described a novel immune-related class of CRC, which may be used for selecting candidate patients with CRC for immunotherapy and tailoring optimal immunotherapeutic treatment.

The role of lncRNAs and circRNAs in the PD-1/PD-L1 pathway in cancer immunotherapy

Cancer immunotherapy has recently shown promising antitumor effects in various types of tumors. Among all immune checkpoints, the PD-1/PD-L1 pathway plays an important role in the immune evasion of tumor cells, making it a potent target in antitumor immunity. Accordingly, antibodies targeting the PD-1/PD-L1 pathway have been developed to attack tumor cells; however, resistance to immune therapy remains to be solved. Hence, identification of the underlying modulators of the PD-1/PD-L1 pathway is of significant importance to understand the mechanisms of antitumor immunotherapy. Long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs) have been identified to regulate the PD-1/PD-L1 pathway, leading to participation in the immune response and immunotherapy. Therefore, this review focuses on the functions of lncRNAs and circRNAs in regulation of the PD-1/PD-L1 axis in tumorigenesis and tumor progression. We hope this review will stimulate research to supply more precise and effective cancer immune checkpoint therapies for a large number of tumors.

P14.53 Immunotherapy in the complex treatment of HGG

BACKGROUND To improve the long-term results of complex treatment of patients with malignant gliomas MATERIAL AND METHODS The long-term results of treatment of 220 patients with malignant gliomas of supratentorial localization (anaplastic astrocytomas, glioblastomas, giant cell glioblastomas, gliosarcomas) were evaluated. Of these patients, in addition to standard treatment methods (surgery, radiation therapy and chemotherapy), 110 patients underwent specific antitumor immunotherapy. In 110 patients, only standard methods were used in the complex treatment structure. Follow-up results were considered follow-up data, and a relapse-free period was also evaluated. RESULTS The implementation of specific antitumor immunotherapy in patients with malignant gliomas was safe and did not lead to an increase in the number of complications compared with the control group. It was revealed that the use of immunotherapy based on autologous dendritic cells, in addition to standard methods of treating patients, increases the average life expectancy (in patients with anaplastic astrocytomas up to 40.5 months (p = 0.001), in patients with glioblastomas up to 21.8 months (p = 0.002)) and the value of the relapse-free period (in patients with anaplastic astrocytomas up to 17.4 months (p = 0.002), in patients with glioblastomas up to 14.3 months (p = 0.003)), provided that three or more courses are carried out. Conducting 1 or 2 courses of immunotherapy does not significantly affect the average life expectancy and median survival of patients. CONCLUSION The development and use in clinical practice of specific antitumor immunotherapy based on autologous dendritic cells seems to be a very promising direction for further research, the development of which will improve the long-term results of treatment of patients.

PTENα functions as an immune suppressor and promotes immune resistance in PTEN-mutant cancer

PTEN is frequently mutated in human cancers and PTEN mutants promote tumor progression and metastasis. PTEN mutations have been implicated in immune regulation, however, the underlying mechanism is largely unknown. Here, we report that PTENα, the isoform of PTEN, remains active in cancer bearing stop-gained PTEN mutations. Through counteraction of CD8+ T cell-mediated cytotoxicity, PTENα leads to T cell dysfunction and accelerates immune-resistant cancer progression. Clinical analysis further uncovers that PTENα-active mutations suppress host immune responses and result in poor prognosis in cancer as relative to PTENα-inactive mutations. Furthermore, germline deletion of Ptenα in mice increases cell susceptibility to immune attack through augmenting stress granule formation and limiting synthesis of peroxidases, leading to massive oxidative cell death and severe inflammatory damage. We propose that PTENα protects tumor from T cell killing and thus PTENα is a potential target in antitumor immunotherapy.