Figure 6 from Selective STING Activation in Intratumoral Myeloid Cells via CCR2-Directed Antibody–Drug Conjugate TAK-500
Year: 2025
Type: other
Abstract: Spatially resolved and quantitative analysis of CCR2 in human NSCLC, PDAC, and CRC. A, Representative multicolor fluorescence micrographs of NSCLC cases with high (left) and low CCR2 protein expression (right). The color code for the markers is indicated within the caption. CCR2 colocalizes with CD11b/CD68 double-positive myeloid cells both within the CK+ tumor epithelium and in the surrounding stroma. Scale bar, 250 µm. B, Expression and distribution of total CCR2 protein levels (all cells) in NSCLC (green bars), PDAC (red bars), and CRC (blue bars). Each column in the histogram indicates the total CCR2 protein level in an individual tumor from the cohort. The chart on the right shows the mean levels of CCR2 protein across the three tumor types. C, Detection of CCR2 positivity in the tumor samples using the visual threshold showed a detectable signal in 94% of NSCLCs (N = 411), 89% of PDACs (N = 228), and 87% of CRCs (N = 350). D, Levels of CCR2 protein measured in the entire tumor tissue sample (total), or selectively in CK+ tumor epithelial cell areas (tumor), in CK− tumor tissue areas (stroma) and in CD11b+ myeloid cells (myeloid) across NSCLC, PDAC, and CRC. E, Levels of CCR2 protein in selected tumor tissue compartments across primary lung adenocarcinomas with activating EGFR (green, n = 26) and KRAS mutations (red, n = 38) and in tumors lacking oncogenic variants in both oncogenes (gray, n = 57). Each dot in the graph represents the score in an individual tumor sample. F, Levels of CD8, PD-L1, CD11c, or XCR1 protein in primary NSCLCs with low or high CCR2 protein levels. Cases were stratified into high/low groups using the median total CCR2 protein scores. G, Representative multicolor fluorescence micrographs of CCR2, tumor, and myeloid cells in CRC cases with microsatellite instability–high (MSI-H; left) and microsatellite stable (MSS) status (right). The color code for the markers is indicated within the caption. The charts on the right show the CCR2 protein levels across the MSI-H (n = 51) and MSS (n = 282) CRC subgroups in the entire tissue area (total) or selectively measured in CK+ epithelial tumor cells (tumor), CK− stromal cells (stromal), or in CD68+ TAMs. *, P < 0.05; **, P < 0.01; ***, P < 0.001; ****, P < 0.0001; ns, not significant with P > 0.05. QIF, quantitative immunofluorescence.
Authors: Vicky A. Appleman, Atsushi Matsuda, Michelle L. Ganno, Dong Mei Zhang, Emily Rosentrater, Angel E. Maldonado Lopez, Angelo Porciuncula, Tiquella Hatten, Camilla L. Christensen, Samantha A. Merrigan, Hong Myung Lee, Min Young Lee, Charlotte I. Wang, Linlin Dong, Jian Huang, Natasha Iartchouk, Jianing Wang, He Xu, Tomoki Yoneyama, Konstantin I. Piatkov, Satyajeet Haridas, Carole E. Harbison, Richard C. Gregory, Alexander Parent, Neil Lineberry, Chris Arendt, Kurt A. Schalper, Adnan O. Abu-Yousif
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
OpenAlex ID: W4410047694