Tumor-infiltrated double-negative regulatory T cells predict outcome of T cell-based immunotherapy in nasopharyngeal carcinoma.

Adoptive cell therapy (ACT) using tumor-infiltrating lymphocytes (TILs) has demonstrated clinical success in solid tumors. We analyze 47 TIL infusion products and 62 pretreatment tumor microenvironments (TMEs) from a randomized phase 2 clinical study of concurrent chemoradiotherapy plus TIL-ACT (NCT02421640). Using single-cell and bulk RNA sequencing along with flow cytometry, we identify 14 CD3 T cell clusters within 26 TIL infusion products: 11 CD3CD8 TILs, 2 CD3CD4 TILs, and 1 CD3CD8CD4 double-negative (DN) TIL.

TOX2 nuclear-cytosol translocation is linked to leukemogenesis of acute T-cell leukemia by repressing TIM3 transcription.

Nuclear factors TOX and TOX2 upregulate TIM3 expression and lead to T-cell exhaustion in malignancies. Here, we demonstrate two distinct TIM3 expression patterns (high & low) with high TOX and TOX2 levels in T-cell acute lymphoblastic leukemia (T-ALL) specimens and cell lines. However, the mechanisms regulated by TOX and TIM3 signaling in leukemogenesis are unclear.

DNA Image Cytometry for Screening the Carcinogenetic Risk of Oral Potential Malignant Disorders.

Oral Submucosal Fibrosis (OSF) and Oral Leukoplakia (OLK) are well-known oral potentially malignant disorders, and cases of Oral Submucosal Fibrosis concomitant Oral Leukoplakia (OSF+OLK) are now being reported clinically. DNA image cytometry is an objective and non-invasive method for monitoring the risk of precancerous lesions in the oral cavity. A total of 111 patients with clinically characterized oral mucosal lesions underwent simultaneous and independent histopathological and DNA imaging cytometry assessments.

Design, synthesis, and evaluation of VHL-based EZH2 degraders for breast cancer.

EZH2 (enhancer of zeste homolog 2) is one of the most important histone methyltransferases (HMTs), and overexpression of EZH2 can lead to proliferation, migration and angiogenesis of tumor cells. But most of EZH2 inhibitors are only effective against some hematologic malignancies and have poor efficacy against solid tumors. Here, we report the design, synthesis, and evaluation of highly potent proteolysis targeting chimeric (PROTACs) small molecules targeting EZH2.