k ras inhibitor 9  (TargetMol)

Journal: Advanced Science

Article Title: Mutant KRAS Drives Immune Evasion by Sensitizing Cytotoxic T‐Cells to Activation‐Induced Cell Death in Colorectal Cancer

doi: 10.1002/advs.202203757

Figure Lengend Snippet: Clinical correlation between mutant KRAS and intratumoral cytotoxic CD8 + T‐cells. A) CD8 immunostaining within tumor tissue and invasive margin in a representative human CRC case carrying mutant KRAS compared to a KRAS wild‐type case. B) Quantification of CD8 + T‐cells within tumor tissues and invasive margin in KRAS mutant (n = 76) and KRAS wild‐type cases (n = 99). C) Statistical analysis of CD8 + T‐cells within tumor tissues in dMMR (n = 56) and pMMR cases (n = 119). D) Statistics of CD8 + T‐cells within the tumor tissues in 76 CRC patients of KRAS mutations (Left panel, Others include KRAS G12C (n = 4), G12R (n = 2), G12S (n = 6), G13C (n = 1), K117N (n = 1), A146T (n = 2), and Q61H (n = 2) mutations), and in 25 CRC patients of dMMR (Middle panel, Others include KRAS G12V (n = 1), K117N (n = 1), A146T (n = 2), and Q61H (n = 2) mutations), and in 51 CRC patients of pMMR (Right panel, Others include KRAS G12C (n = 4), G12R (n = 2), G12S (n = 6), and G13C (n = 1) mutations). E) Pearson's correlation analysis between KRAS expression levels and CD8 + T‐cell density in CRC tissues. Scare bars, 100 µm (A), *** P ≤ 0.001, and ns indicates P > 0.05, by two‐tailed Student's t ‐test (B,C), one‐way ANOVA (D), or Person's correlation analysis (E).

Article Snippet: The KRAS G12C inhibitor AMG 510 (Selleck) was given daily through oral gavage at 30 mL kg −1 .

Techniques: Mutagenesis, Immunostaining, Expressing, Two Tailed Test

Journal: Advanced Science

Article Title: Mutant KRAS Drives Immune Evasion by Sensitizing Cytotoxic T‐Cells to Activation‐Induced Cell Death in Colorectal Cancer

doi: 10.1002/advs.202203757

Figure Lengend Snippet: Susceptibility of tumor‐specific CTLs to AICD in KRAS mutant CRC. A) Flow cytometry analysis of the migratory abilities of CTLs from KRAS wild type versus mutant tumors (n = 5). B–E) ELISAs for CXCL9, CXCL10, CXCL12, and CCL22 expression in KRAS wild type versus mutant tumors (n = 5). F–H) ELISAs for FasL, TNF, and TRAIL expression in KRAS wild type versus mutant tumor cells (n = 5). I) Tumor‐specific CTL apoptosis induced by autologous primary tumor cells or anti‐CD3. Numerical values denote the percentage of annexin V + cells (mean ± SD). J,K) Statistics of autologous tumor cells‐ or anti‐CD3‐induced specific apoptotic rates of tumor‐specific CTLs from KRAS wild type versus mutant tumors (n = 20). L,M) Statistics of autologous tumor cells‐ or anti‐CD3‐induced specific apoptotic rates of tumor‐specific CTLs from 20 tumors of different types of KRAS mutations (Others include KRAS G12C (n = 2), G12R (n = 1), and G13C (n = 1) mutations). N–P) ELISAs for Fas, TNFR2, and TRAILER expression in CTLs from KRAS wild type versus mutant tumors (n = 5). *** P ≤ 0.001, and ns indicates P > 0.05, by two‐tailed Student's t ‐test (A–H,J,K,N–P) or one‐way ANOVA (L,M).

Article Snippet: The KRAS G12C inhibitor AMG 510 (Selleck) was given daily through oral gavage at 30 mL kg −1 .

Techniques: Mutagenesis, Flow Cytometry, Expressing, Two Tailed Test