Distinct pattern of TP53 mutations in human immunodeficiency virusâ related head and neck squamous cell carcinoma

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142251/1/cncr31063.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/142251/2/cncr31063_am.pd

9p21 loss confers a cold tumor immune microenvironment and primary resistance to immune checkpoint therapy

Immune checkpoint therapy (ICT) provides substantial clinical benefits to cancer patients, but a large proportion of cancers do not respond to ICT. To date, the genomic underpinnings of primary resistance to ICT remain elusive. Here, we performed immunogenomic analysis of data from TCGA and clinical trials of anti-PD-1/PD-L1 therapy, with a particular focus on homozygous deletion of 9p21.3 (9p21 loss), one of the most frequent genomic defects occurring in ~13% of all cancers. We demonstrate that 9p21 loss confers "cold" tumor-immune phenotypes, characterized by reduced abundance of tumor-infiltrating leukocytes (TILs), particularly, T/B/NK cells, altered spatial TILs patterns, diminished immune cell trafficking/activation, decreased rate of PD-L1 positivity, along with activation of immunosuppressive signaling. Notably, patients with 9p21 loss exhibited significantly lower response rates to ICT and worse outcomes, which were corroborated in eight ICT trials of >1,000 patients. Further, 9p21 loss synergizes with PD-L1/TMB for patient stratification. A "response score" was derived by incorporating 9p21 loss, PD-L1 expression and TMB levels in pre-treatment tumors, which outperforms PD-L1, TMB, and their combination in identifying patients with high likelihood of achieving sustained response from otherwise non-responders. Moreover, we describe potential druggable targets in 9p21-loss tumors, which could be exploited to design rational therapeutic interventions

Conductive Polymer Coated Threads as Electrical Interconnect in e-Textiles

An organic polymer electrical interconnect is demonstrated. The ionomer mixture poly(3,4-ethylenedioxythiophene): poly(styrenesulfonate) (PEDOT:PSS; 1:2.5, w:w) was cast onto silk fibers from a 50:50 (v:v) ethylene glycol solution by a dip-coating process. Dynamic mechanical analysis (DMA) results show that Young’s modulus and mechanical strength are maintained during the coating process from acidic solution (pH ∼1). DMA dynamic temperature scans reveal two new thermal transitions once PEDOT:PSS is applied to the silk fiber, and they are assigned to the glass transition temperature (59 °C) and melting point (146 °C) of the ionomer pair. Electrical conductivities of 8.5 S/cm were achieved with four cycles of the dip-coating process, only 10x less than Ag-coated thread control samples. SEM imaging of the PEDOT:PSS-coated fibers show slight texturing to the fibers due to the coating, as well as significant charging in the uncoated samples when compared to PEDOT:PSS-coated samples. The conductive fibers fabricated by this process were successfully applied as electrical interconnects in flexible, fully functional 555 timer circuits stitched into fabric substrates