Circulating kidney injury molecule-1 (KIM-1) and association with outcome to adjuvant immunotherapy in renal cell carcinoma.

Background: Adjuvant immunotherapy is currently the standard of care for patients with resected renal cell carcinoma (RCC) at increased risk of recurrence, but there are no biomarkers available to guide treatment. Kidney injury molecule-1 (KIM-1) has previously been described as a potential circulating biomarker in renal cell carcinoma.

Patients And Methods: Biomarkers and outcomes among patients who participated in a randomized phase III trial of adjuvant atezolizumab versus placebo in resected RCC (IMmotion010) were evaluated.

Digital Versus Manual PD-L1 Scoring in Advanced NSCLC From the IMpower110 and IMpower150 Trials.

Introduction: Treatment selection in patients with advanced NSCLC is based on programmed death-ligand 1 (PD-L1) expression, which is usually scored manually and is subject to intra- and inter-pathologist variability. A PD-L1 clone-agnostic artificial intelligence (AI) model for AI-based measurement of PD-L1 (AIM-PD-L1) was developed and assessed in advanced NSCLC using clinical samples from two phase 3 trials.

Methods: IMpower110 evaluated atezolizumab versus chemotherapy in PD-L1-positive metastatic, stage IV, squamous or nonsquamous NSCLC.

Heterogeneity of CD8 T-Cell Changes in Advanced Melanomas After Initiation of Immunotherapy.

Whole-body CD8 T-cell PET imaging can detect spatial and temporal localization of CD8 T cells. To obtain insight into early CD8 T-cell response to immunotherapy in patients with melanoma, a highly immunogenic tumor, we performed serial PET imaging with the 1-armed CD8 antibody tracer ZED88082A. Immunotherapy-naïve adult patients with stage IV melanoma underwent PET scanning 2 d after receiving 10 mg of ZED88082A intravenously at baseline and 6-8 wk after initiation of standard-of-care immunotherapy.

Precision targeting of β-catenin induces tumor reprogramming and immunity in hepatocellular cancers.

First-line immune checkpoint inhibitor (ICI) combinations show responses in subsets of hepatocellular carcinoma (HCC) patients. Nearly half of HCCs are Wnt-active with mutations in CTNNB1 (encoding for β-catenin), AXIN1/2, or APC, and demonstrate heterogeneous and limited benefit to ICI due to an immune excluded tumor microenvironment. We show significant tumor responses in multiple β-catenin-mutated immunocompetent HCC models to a novel siRNA encapsulated in lipid nanoparticle targeting CTNNB1 (LNP-CTNNB1).

IL-27 elicits a cytotoxic CD8 T cell program to enforce tumour control.

Although cytotoxic CD8 T lymphocytes (CTLs) are essential for anti-tumour immunity, they are frequently dysfunctional in tumours. Cytokines that sustain CTL activity are attractive for cancer immunotherapy, but avoiding inflammatory toxicity remains a challenge for their clinical use. Here we show that expression of a CTL signature is strongly associated with IL27 expression in human and mouse tumours.