Cancer Science

Extracellular vesicles (EVs) derived from myeloma cells could potentially induce T cell exhaustion via the increase of the frequency of immune checkpoint marker-positive CD8+ T cells and might thereby suppress T cell function. In addition, this immune escape mechanism from cytotoxic T cells is supported by the findings on SPHK1/S1P signaling from SPHK1-packaged EVs.

In this multicenter, single-arm, open-label phase II trial, patients with HER2-positive breast cancer who had previously received chemotherapy with taxanes or anthracyclines were enrolled to receive pyrotinib combined with nab-paclitaxel, and the results demonstrated promising efficacy with an acceptable safety profile.

Acute temporal edema, which can potentially obstruct the airway, is the most common adverse effect associated with near-infrared photoimmunotherapy (NIR-PIT) of head and neck cancer. Leveraging the chemical mechanisms of NIR-PIT, vitamin C has been shown to suppress such edema and enhance cytotoxicity by quenching reactive oxygen species and donating protons. This study demonstrates that the administration of vitamin C during NIR-PIT effectively suppresses local edema while simultaneously enhancing therapeutic efficacy, all without compromising the host immune response.

This study compared male breast cancer (MBC) and female breast cancer (FBC) survival using data from Japanese population-based cancer registries diagnosed between 1993 and 2011. The findings reveal that MBC survival is comparable to FBC, with no significant sex-based differences in 5- and 10-year net survival across period, age, stage, and histological groups. These results provide important insights into the similarities in survival outcomes between MBC and FBC in Japan.

()-D-Tox peptide binding to the ligands triggers their internalization via clathrin-mediated endocytosis. Intracellular presence of ()-D-Tox peptide induces a transient loss of mitochondrial membrane integrity and oligomerization of MLKL. Translocation of the oligomers to the plasma membrane causes a leakage of the cytosolic content and ultimately leads to cell death.

This review summarizes the current understanding of cytotoxic CD8⁺ T cell subset differentiation under tumor progression and highlights the crucial role of chronic CD8⁺ T cell responses in anti-tumor immunity. CD69 is an important regulator of chronic CD8⁺ T cell response that contributes to the induction of the Tox gene via calcineurin/NFAT signaling.

DNA in the circulating extracellular vesicle (evDNA) has superior potential for detecting KRAS mutations compared with circulating tumor DNA, possibly because evDNA comprises very long, undamaged DNA strands. The analysis using evDNA demonstrated that heterogeneity related to KRAS exists at a higher frequency than we had anticipated. Furthermore, it was suggested that colorectal cancer patients with higher levels of evDNA may have a poorer prognosis.

There remain outstanding gaps between the negative results from clinical trials and the actual potential of the immune system for glioblastoma. To bridge this crucial gap, we collaborated with Dr. Mariko Takahashi, an expert in immunobiology and drug development, and Dr. James J. Moon, an expert in nanotechnology and immunoengineering, each of whom played a key role in the conceptualization and development of this manuscript. We first discussed the status of clinical trials against GBM and summarized recent studies on (1) targeting the systemic immune system, (2) enhancing tumor immunogenicity, and (3) targeting extra-parenchymal brain immune niches.

It demonstrates the tumor-suppressive roles of BAP1 in CCA: BAP1 significantly inhibits CCA cell proliferation and tumor progression. It identifies VCP as a key upstream regulator mediating BAP1 homeostasis: VCP binds to BAP1 and promotes the latter's ubiquitination degradation via the ubiquitin-proteasome pathway. It offers a novel therapeutic target for CCA treatment: targeting VCP With its inhibitors significantly inhibited CCA growth by blocking BAP1 ubiquitination degradation in vitro/in vivo.

The effect of cetuximab and epacadostat combinative therapy on CRC cells.

Oral squamous cell carcinoma (OSCC), the most common type of oral cancer, has a poor prognosis. This study found high Ephrin type-B receptor 4 (EPHB4) expression, mainly localized on the tumor cell membrane, in most OSCC cases, suggesting EPHB4 as a promising target for chimeric antigen receptor (CAR) T cell therapy. Intratumoral injection of EPHB4-specific CAR-T cells suppressed tumor growth in SAS and PDX mouse models, accompanied by reduced EPHB4 expression, decreased carcinoma area, and CAR-T cell accumulation within the tumor tissues.

TFRC may serve as a critical prognostic indicator for risk assessment in EC patients and propose TFRC as a promising therapeutic target to impede EC progression. The upregulation of TFRC-mediated iron absorption facilitated the proliferation of EC, suggesting that iron chelators had the potential to be a promising therapeutic agent for the treatment of EC. The combination of iron chelators and mTOR inhibitors may become a novel treatment strategy for patients with advanced and recurrent EC in the future.

High antigenicity of T_reg cells confers resistance to anti-PD-1 mAb monotherapy via high PD-1 expression in T_reg cells. Resistance to anti-PD-1 mAb monotherapy via high PD-1 expression in T_reg cells can be overcome by combination therapy with an anti-CTLA-4 mAb. PD-1⁺ T_reg cells in the TME and T_reg cell antigens may be predictive biomarkers for combination therapy with anti-PD-1 and anti-CTLA-4 mAbs.

We propose a novel CHI3L1-associated vascular phenotype classification for glioma, each characterized by unique tumor features, including immune cell infiltration, metabolic reprogramming, and genomic alterations. We identified CHI3L1-associated vascular signatures that reflect tumor angiogenesis and immunosuppression. We devised a vascular-related risk (VR) score, with the high-VR-score group exhibiting enhanced angiogenic activity, reduced immune response, immunotherapy resistance, and poorer clinical outcomes.

Our findings offer new insights into the abnormal accumulation of TRAF6 in HCC, wherein decreased SPOP expression leads to impaired degradation of TRAF6, consequently promoting activation of the NF-κB pathway and tumor progression (Graphical abstract). These insights enhance the comprehension of the pathological progression of HCC and inform the future development of therapeutic agents for its treatment.

IL-34 and its receptors.

Among cancer-associated antigens, ganglioside GD2 is the most crucial and essential carbohydrate antigen as a modulator of malignant signals and as a target of immunotherapy for refractory cancers. In particular, GD2 is now believed to be a marker of cancer stem cells and to be essentially involved in the features of cancer stemness.

We have developed a silylated derivative of decitabine, OR-2100, which is resistant to degradation by cytidine deaminase and orally bioavailable. In this article, we review the current status of DNA demethylating agents for treating hematological malignancies, with a focus on OR-2100.

We conducted a Phase I trial of CBA-1205, a novel monoclonal antibody targeting DLK1, in advanced solid tumors, demonstrating safety and tolerability with no dose-limiting toxicities. Preliminary efficacy was observed, with six patients achieving stable disease for over 6 months, and sDLK1 was identified as a potential biomarker associated with response.

Identifying actionable mutations and gene fusions of KRAS wild-type pancreatic ductal adenocarcinoma offers significant potential for targeted and immune-based therapies, by retrospective study and genomic profiling analysis, together with comparative analysis of TCGA-PAAD data. Specifically, HRD, epigenetic regulatory gene mutations and actionable CCDC6-RET, and NTRK3 fusions are expected to guide personalized precision therapy for KRAS-WT PDAC and need further investigation in larger cohorts.