An AI-assisted integrated, scalable, single-cell phenomic-transcriptomic platform to elucidate intratumor heterogeneity against immune response.

We present a novel framework combining single-cell phenotypic data with single-cell transcriptomic analysis to identify factors underpinning heterogeneity in antitumor immune response. We developed a pairwise, tumor-immune discretized interaction assay between natural killer (NK-92MI) cells and patient-derived head and neck squamous cell carcinoma (HNSCC) cell lines on a microfluidic cell-trapping platform. Furthermore we generated a deep-learning computer vision algorithm that is capable of automating the acquisition and analysis of a large, live-cell imaging data set (>1 million) of paired tumor-immune interactions spanning a time course of 24 h across multiple HNSCC lines (n = 10). Finally, we combined the response data measured by Kaplan-Meier survival analysis against NK-mediated killing with downstream single-cell transcriptomic analysis to interrogate molecular signatures associated with NK-effector response. As proof-of-concept for the proposed framework, we efficiently identified MHC class I-driven cytotoxic resistance as a key mechanism for immune evasion in nonresponders, while enhanced expression of cell adhesion molecules was found to be correlated with sensitivity against NK-mediated cytotoxicity. We conclude that this integrated, data-driven phenotypic approach holds tremendous promise in advancing the rapid identification of new mechanisms and therapeutic targets related to immune evasion and response.

Inappropriate tuberculosis treatment regimens in Chinese tuberculosis hospitals.

This investigation of tuberculosis (TB) treatment regimens in 6 TB hospitals in China showed that only 18% of patients with new cases and 9% of patients with retreatment cases were prescribed standard TB treatment regimens. Adherence to treatment guidelines needs to be improved in TB hospitals to control multidrug-resistant TB in China.

Multidrug-resistant tuberculosis, People's Republic of China, 2007-2009.

We conducted a case-control study to investigate risk factors for multidrug-resistant tuberculosis (MDR TB) in the People's Republic of China. Genotyping analysis was used to estimate the percentage of cases from recent transmission among 100 MDR TB case-patients hospitalized during April 2007-July 2009. Molecular subtyping of isolates showed that 41% of MDR TB strains clustered. Beijing genotype was found in 94% of the MDR TB isolates and 79% of the pan-susceptible isolates. In multivariate analysis, MDR TB was independently associated with Beijing genotype, retreatment for TB, symptoms lasting >3 months before first evaluation at the hospital, lack of health insurance, and being a farmer (vs. being a student). MDR TB was associated with Beijing genotype and lower socioeconomic status. A large percentage of MDR TB cases seemed to result from recent transmission. Early detection, effective treatment, and infection control measures for MDR TB are needed to reduce transmission.