Digital spatial profiling of melanoma shows CD95 expression in immune cells is associated with resistance to immunotherapy.

Although immune checkpoint inhibitor (ICI) therapy has dramatically improved outcome for metastatic melanoma patients, many patients do not benefit. Since adverse events may be severe, biomarkers for resistance would be valuable, especially in the adjuvant setting. We performed high-plex digital spatial profiling (DSP) using the NanoString GeoMx® on 53 pre-treatment specimens from ICI-treated metastatic melanoma cases.

Outcomes With Combination Pembrolizumab and Axitinib in Second and Further Line Treatment of Metastatic Renal Cell Carcinoma.

Introduction: Combination immune checkpoint inhibitors (ICI) and vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGF-R-TKI), including pembrolizumab/axitinib, are approved for first-line treatment of metastatic renal cell carcinoma (mRCC). Pembrolizumab/axitinib is associated with superior progression free survival (PFS), objective response rate (ORR), and overall survival over sunitinib. However, to date, the activity and safety of pembrolizumab/axitinib in later lines of therapy has not been reported.

Baseline gene expression profiling determines long-term benefit to programmed cell death protein 1 axis blockade.

Treatment with immune checkpoint inhibitors has altered the course of malignant melanoma, with approximately half of the patients with advanced disease surviving for more than 5 years after diagnosis. Currently, there are no biomarker methods for predicting outcome from immunotherapy. Here, we obtained transcriptomic information from a total of 105 baseline tumor samples comprising two cohorts of patients with advanced melanoma treated with programmed cell death protein 1 (PD-1)-based immunotherapies.

Immune Checkpoint Inhibitor-Induced Hypophysitis and Patterns of Loss of Pituitary Function.

Background: Immune checkpoint inhibitors (ICI) are clinically active across multiple tumor types but the associated immune-related adverse events (irAEs) lead to treatment delays or discontinuation and negatively impact quality-of-life. Hypophysitis is often a permanent irAE that may affect multiple pituitary hormonal axes. Here we comprehensively characterize our institution's clinical experience with ICI-induced hypophysitis and the associated patterns of pituitary function loss.

Inhibition of renalase drives tumour rejection by promoting T cell activation.

Background: Although programmed cell death protein 1 (PD-1) inhibitors have revolutionised treatment for advanced melanoma, not all patients respond. We previously showed that inhibition of the flavoprotein renalase (RNLS) in preclinical melanoma models decreases tumour growth. We hypothesised that RNLS inhibition promotes tumour rejection by effects on the tumour microenvironment (TME).

KDM5B promotes immune evasion by recruiting SETDB1 to silence retroelements.

Tumours use various strategies to evade immune surveillance. Immunotherapies targeting tumour immune evasion such as immune checkpoint blockade have shown considerable efficacy on multiple cancers but are ineffective for most patients due to primary or acquired resistance. Recent studies showed that some epigenetic regulators suppress anti-tumour immunity, suggesting that epigenetic therapies could boost anti-tumour immune responses and overcome resistance to current immunotherapies.

A Phase I Study of APX005M and Cabiralizumab with or without Nivolumab in Patients with Melanoma, Kidney Cancer, or Non-Small Cell Lung Cancer Resistant to Anti-PD-1/PD-L1.

Purpose: PD-1/PD-L1 inhibitors are approved for multiple tumor types. However, resistance poses substantial clinical challenges.

Patients And Methods: We conducted a phase I trial of CD40 agonist APX005M (sotigalimab) and CSF1R inhibitor cabiralizumab with or without nivolumab using a 3+3 dose-escalation design (NCT03502330).

Analysis of multispectral imaging with the AstroPath platform informs efficacy of PD-1 blockade.

Next-generation tissue-based biomarkers for immunotherapy will likely include the simultaneous analysis of multiple cell types and their spatial interactions, as well as distinct expression patterns of immunoregulatory molecules. Here, we introduce a comprehensive platform for multispectral imaging and mapping of multiple parameters in tumor tissue sections with high-fidelity single-cell resolution. Image analysis and data handling components were drawn from the field of astronomy.

Clinical Significance of PDCD4 in Melanoma by Subcellular Expression and in Tumor-Associated Immune Cells.

Little is known about the subcellular localization and function of programmed cell death 4 (PDCD4) in melanoma. Our past studies suggest PDCD4 interacts with Pleckstrin Homology Domain Containing A5 (PLEKHA5) to influence melanoma brain metastasis outcomes, as high intracranial PDCD4 expression leads to improved survival. We aimed to define the subcellular distribution of PDCD4 in melanoma and in the tumor microenvironment during neoplastic progression and its impact on clinical outcomes.

Mycophenolate as Primary Treatment for Immune Checkpoint Inhibitor Induced Acute Kidney Injury in a Patient with Concurrent Immunotherapy-Associated Diabetes: A Case Report.

Immune checkpoint inhibitors enhance T cell response against malignant cells and are standard of care in many tumor types. Disinhibition of cytotoxic T cells in normal organs and inhibition of regulatory T cells can lead to immune-related adverse events. Here we describe a 60-year-old man with metastatic melanoma treated with three cycles of nivolumab and ipilimumab.

Circulating clonally expanded T cells reflect functions of tumor-infiltrating T cells.

Understanding the relationship between tumor and peripheral immune environments could allow longitudinal immune monitoring in cancer. Here, we examined whether T cells that share the same TCRαβ and are found in both tumor and blood can be interrogated to gain insight into the ongoing tumor T cell response. Paired transcriptome and TCRαβ repertoire of circulating and tumor-infiltrating T cells were analyzed at the single-cell level from matched tumor and blood from patients with metastatic melanoma.

Automated Assay of a Four-Protein Biomarker Panel for Improved Detection of Ovarian Cancer.

: Mortality from ovarian cancer remains high due to the lack of methods for early detection. The difficulty lies in the low prevalence of the disease necessitating a significantly high specificity and positive-predictive value (PPV) to avoid unneeded and invasive intervention. Currently, cancer antigen- 125 (CA-125) is the most commonly used biomarker for the early detection of ovarian cancer.

Non-Small-cell Lung Cancer Patients With Adenocarcinoma Morphology Have a Better Outcome Compared With Patients Diagnosed With Non-Small-cell Lung Cancer Favor Adenocarcinoma.

Background: Non-small-cell lung cancer (NSCLC) includes 2 major histologic subtypes: squamous cell carcinoma and non-squamous carcinoma, mainly adenocarcinoma, a distinction that carries significant clinical and therapeutic implications. NSCLC is diagnosed as adenocarcinoma or as squamous cell carcinoma on the basis of histologic parameters. However, when morphology is inconclusive, tumors with immunohistochemistry (IHC) findings characteristic of adenocarcinoma are referred to as "NSCLC favor adenocarcinoma" (NFA).

Improving posttransplantation survival of human ovarian tissue by treating the host and graft.

Objective: To improve posttransplantation survival of frozen-thawed human ovarian tissue in immunodeficient mice.

Design: Histologic study of transplanted human ovaries after treating the host and graft.

Setting: Infertility unit, university-affiliated tertiary medical center.