Background Human papillomavirus (HPV)-driven cancers include head and neck squamous cell carcinoma and cervical cancer and represent approximately 5% of all cancer cases worldwide. Standard-of-care chemotherapy, radiotherapy, and immune checkpoint inhibitors (ICIs) are associated with adverse effects and limited responses in patients with HPV-driven cancers. The integration of targeted therapies with ICIs may improve outcomes.… Continue reading Targeted inhibition of Aurora kinase A promotes immune checkpoint inhibition efficacy in human papillomavirus-driven cancers
Tag: Adaptive Immunity
Differential impact of TIM-3 ligands on NK cell function
Background The transmembrane protein T-cell immunoglobulin and mucin-domain containing molecule 3 (TIM-3) is an immune checkpoint receptor that is expressed by a variety of leukocyte subsets, particularly in the tumor microenvironment. An effective TIM-3-targeting therapy should account for multiple biological factors, including the disease setting, the specific cell types involved and their varying sensitivities to… Continue reading Differential impact of TIM-3 ligands on NK cell function
Divergent response to radio-immunotherapy is defined by intrinsic features of the tumor microenvironment
Background Treatment with immunotherapy can elicit varying responses across cancer types, and the mechanistic underpinnings that contribute to response vrsus progression remain poorly understood. However, to date there are few preclinical models that accurately represent these disparate disease scenarios. Methods Using combinatorial radio-immunotherapy consisting of PD-1 blockade, IL2Rβ biased signaling, and OX40 agonism we were… Continue reading Divergent response to radio-immunotherapy is defined by intrinsic features of the tumor microenvironment
Structural insights into hybridoma-derived neutralizing monoclonal antibodies against Omicron BA.5 and XBB.1.16 variants of SARS-CoV-2
Lethal clinical outcome and chemotherapy and immunotherapy resistance in patients with urothelial carcinoma with MDM2 amplification or overexpression
Background The E3 ubiquitin ligase murine double minute 2 (MDM2) binds the p53 transcriptional activation domain and acts as a potent inhibitor of TP53 pathway, one of the three most crucial oncogenic pathways in urothelial carcinoma (UC). However, the clinical significance and impact on tumor immune contexture of MDM2 amplification in UC remain unclear. Methods… Continue reading Lethal clinical outcome and chemotherapy and immunotherapy resistance in patients with urothelial carcinoma with MDM2 amplification or overexpression
XCL1-secreting CEA CAR-T cells enhance endogenous CD8+ T cell responses to tumor neoantigens to confer a long-term antitumor immunity
Background Therapeutic efficacy of carcinoembryonic antigen (CEA)-specific chimeric antigen receptor (CAR) T cells against colorectal cancer (CRC) remains limited due to the unique characteristics and distinct microenvironments of tumor tissues. We modified CEA-specific CAR-T cells, aiming to stimulate endogenous CD8+ T cell responses against neoantigens that were derived from CEA-positive tumors destroyed by the CAR… Continue reading XCL1-secreting CEA CAR-T cells enhance endogenous CD8+ T cell responses to tumor neoantigens to confer a long-term antitumor immunity
GP73 reinforces cytotoxic T-cell function by regulating HIF-1{alpha} and increasing antitumor efficacy
Background Immunotherapy that targets immune checkpoints has achieved revolutionary success, but its application in solid tumors remains limited, highlighting the need for reliable enhancement of the efficacy of immunotherapy. Golgi protein 73 (GP73), a Golgi membrane protein, has been implicated in various cellular processes, including immune regulation. Recent studies suggested that GP73 may play a… Continue reading GP73 reinforces cytotoxic T-cell function by regulating HIF-1{alpha} and increasing antitumor efficacy
Lipid metabolic remodeling delays senescence of T cells to potentiate their immunity against solid tumors
Background Tumor cells can drive the senescence of effector T cells by unbalancing their lipid metabolism, thereby limiting adoptive T cell therapy and contributing to tumor immune evasion. Our objective is to provide a feasible strategy for enhancing T cell treatment efficacy against solid tumors. Methods In this study, liposomal arachidonyl trifluoromethyl ketone (ATK) was… Continue reading Lipid metabolic remodeling delays senescence of T cells to potentiate their immunity against solid tumors
Novel and potent MICA/B antibody is therapeutically effective in KRAS LKB1 mutant lung cancer models
Background Concurrent KRAS LKB1 (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… Continue reading Novel and potent MICA/B antibody is therapeutically effective in KRAS LKB1 mutant lung cancer models
CREB3L1 facilitates pancreatic tumor progression and reprograms intratumoral tumor-associated macrophages to shape an immunotherapy-resistance microenvironment
Background To date, a growing body of evidence suggests that unfolded protein response (UPR) sensors play a vital role in carcinogenesis. However, it remains unclear whether they are involved in pancreatic ductal adenocarcinoma (PDAC) and how they relate to clinical outcomes. This study aims to investigate the biological function and mechanism of how a novel… Continue reading CREB3L1 facilitates pancreatic tumor progression and reprograms intratumoral tumor-associated macrophages to shape an immunotherapy-resistance microenvironment