Supplementary Figure S7 from Resistance to Durvalumab and Durvalumab plus Tremelimumab Is Associated with Functional STK11 Mutations in Patients with Non–Small Cell Lung Cancer and Is Reversed by STAT3 Knockdown
Year: 2023
Type: supplementary-materials
Abstract: Characterization of STAT3 phosphorylation in the CT26 STK11 KO model and from primary human NSCLC tumors. (A) Representative multispectral fluorescence imaging of phosphorylated murine STAT3 (pSTAT3), CD45, CD163, and nuclei (DAPI), as indicated, with quantification of positive cells per mm2 in CT26 tumors. 26C16 STK11 KI indicates CT26 STK11 KO clone 26C16 engineered to re-express WT STK11. (B) Normalized protein expression levels of human STAT3 phosphorylated at tyrosine 705 (Y705) from STK11mut and STK11wt samples based on RPPA data from the TCGA database (left). Levels of human STAT3 RNA expression in samples from TCGA (right). (C) pSTAT3 in tumor cells from primary human NSCLC PDX models. Mean percentages of pSTAT3+ cells were identified among human mitochondria-positive tumor cells from duplicate IHC samples for each STK11mut and STK11wt PDX sample as indicated (left). A statistically significant difference in the mean percentage of pSTAT3+ tumor cells was observed (right; two-tailed p-value calculated using a Mann-Whitney test). (D) IHC results from STK11mut NSCLC PDX sample LG0654 and STK11wt NSCLC PDX sample LG0567, which represented the extremes of tumor pSTAT3 IHC signal in tested samples.
Authors: Nabendu Pore, Song Wu, Nathan Standifer, Maria Jure-Kunkel, Melissa de los Reyes, Yashaswi Shrestha, Rebecca Halpin, Raymond Rothstein, Kathy Mulgrew, Stephen Blackmore, Philip Martin, John Meekin, Matthew Griffin, Ina Bisha, Theresa A. Proia, Ricardo J. Miragaia, Ronald Herbst, Ashok Gupta, Shaad E. Abdullah, Rajiv Raja, Melanie M. Frigault, J. Carl Barrett, Phillip A. Dennis, Maria Libera Ascierto, Michael D. Oberst
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
OpenAlex ID: W4362559723