Novel and potent MICA/B antibody is therapeutically effective in mutant lung cancer models.

Background: Concurrent (STK11, KL) mutant non-small cell lung cancers (NSCLC) do not respond well to current immune checkpoint blockade therapies, however targeting major histocompatibility complex class I-related chain A or B (MICA/B), could pose an alternative therapeutic strategy through activation of natural killer (NK) cells.

Methods: Expression of NK cell activating ligands in NSCLC cell line and patient data were analyzed. Cell surface expression of MICA/B in NSCLC cell lines was determined through flow cytometry while ligand shedding in both patient blood and cell lines was determined through ELISA.

A novel and potent MICA/B antibody is therapeutically effective in mutant lung cancer models.

Concurrent (STK11, KL) mutant Non-Small Cell Lung Cancers (NSCLC) is particularly difficult to treat and does not respond well to current immune checkpoint blockade (ICB) therapies. This is due to numerous mechanisms including low antigen presentation limiting T cell mediated killing. To activate anti-tumor immunity, we targeted tumor cell - natural killer (NK) cell interactions.

A telomere-targeting drug depletes cancer initiating cells and promotes anti-tumor immunity in small cell lung cancer.

There are few effective treatments for small cell lung cancer (SCLC) underscoring the need for innovative therapeutic approaches. This study focuses on exploiting telomerase, a critical SCLC dependency as a therapeutic target. A prominent characteristic of SCLC is their reliance on telomerase activity, a key enzyme essential for their continuous proliferation.

Loss of p53 and mutational heterogeneity drives immune resistance in an autochthonous mouse lung cancer model with high tumor mutational burden.

The role of tumor mutational burden (TMB) in shaping tumor immunity is a key question that has not been addressable using genetically engineered mouse models (GEMMs) of lung cancer. To induce TMB in lung GEMMs, we expressed an ultra-mutator variant of DNA polymerase-E (POLE) in lung epithelial cells. Introduction of Pole allele into Kras and Kras; p53 (KP) models significantly increase their TMB.

Tumor intrinsic and extrinsic functions of CD73 and the adenosine pathway in lung cancer.

The adenosine pathway is an exciting new target in the field of cancer immunotherapy. CD73 is the main producer of extracellular adenosine. Non-small cell lung cancer (NSCLC) has one of the highest CD73 expression signatures among all cancer types and the presence of common oncogenic drivers of NSCLC, such as mutant epidermal growth factor receptor (EGFR) and KRAS, correlate with increased CD73 expression.

The anti-cancer effect of retinoic acid signaling in CRC occurs via decreased growth of ALDH+ colon cancer stem cells and increased differentiation of stem cells.

Background: Tumorigenesis is driven by stem cell (SC) overpopulation. Because ALDH is both a marker for SCs in many tissues and a key enzyme in retinoid acid (RA) signaling, we studied RA signaling in normal and malignant colonic SCs.

Hypothesis: RA signaling regulates growth and differentiation of ALDH+ colonic SCs; dysregulation of RA signaling contributes to SC overpopulation and colorectal cancer (CRC) development.

Increased Musashi-2 and Decreased NUMB Protein Levels Observed in Human Colorectal Cancer are reverted to Normal Levels by ATRA-Induced Cell Differentiation.

Background: Musashi stem cell (SC) proteins (MSI-1 & MSI-2) are known to become over expressed during colorectal tumorigenesis in humans and mice. MSI-1 overexpression induces tumorigenesis through Notch activation via inactivation of NUMB. Previous studies also show that MSI-2 overexpression in mice induces intestinal tumorigenesis but the mechanism is independent of NUMB.