The role of the CXCL12/CXCR4 axis in the immunotherapy of non-small cell lung cancer.

Introduction: Peripheral blood mononuclear cells (PBMCs) trafficking is regulated by chemokines, which modulate leukocyte migration toward tumors and may collaborate in the efficacy of immunotherapy. In our study, we investigated whether the CXCL12/CXCR4 axis plays a role in the efficacy of immunotherapy in non-small cell lung cancer (NSCLC) by analyzing CXCR4 expression for CXCR4 in peripheral blood (PB), and the expression of its ligand CXCL12 in tumor.

Methods: We identified PBMCs expressing CXCR4 using flow cytometry in a prospective cohort of NSCLC patients before starting anti-PD-1 immunotherapy.

Spatial multiomics map of trophoblast development in early pregnancy.

The relationship between the human placenta-the extraembryonic organ made by the fetus, and the decidua-the mucosal layer of the uterus, is essential to nurture and protect the fetus during pregnancy. Extravillous trophoblast cells (EVTs) derived from placental villi infiltrate the decidua, transforming the maternal arteries into high-conductance vessels. Defects in trophoblast invasion and arterial transformation established during early pregnancy underlie common pregnancy disorders such as pre-eclampsia.

Peripheral Blood Mononuclear Cells Predict Therapeutic Efficacy of Immunotherapy in NSCLC.

In lung cancer immunotherapy, biomarkers to guide clinical decisions are limited. We now explore whether the detailed immunophenotyping of circulating peripheral blood mononuclear cells (PBMCs) can predict the efficacy of anti-PD-1 immunotherapy in patients with advanced non-small-cell lung cancer (NSCLC). We determined 107 PBMCs subpopulations in a prospective cohort of NSCLC patients before starting single-agent anti-PD-1 immunotherapy (study group), analyzed by flow cytometry.

Stratification of radiosensitive brain metastases based on an actionable S100A9/RAGE resistance mechanism.

Whole-brain radiotherapy (WBRT) is the treatment backbone for many patients with brain metastasis; however, its efficacy in preventing disease progression and the associated toxicity have questioned the clinical impact of this approach and emphasized the need for alternative treatments. Given the limited therapeutic options available for these patients and the poor understanding of the molecular mechanisms underlying the resistance of metastatic lesions to WBRT, we sought to uncover actionable targets and biomarkers that could help to refine patient selection. Through an unbiased analysis of experimental in vivo models of brain metastasis resistant to WBRT, we identified activation of the S100A9-RAGE-NF-κB-JunB pathway in brain metastases as a potential mediator of resistance in this organ.

A comprehensive database for integrated analysis of omics data in autoimmune diseases.

Background: Autoimmune diseases are heterogeneous pathologies with difficult diagnosis and few therapeutic options. In the last decade, several omics studies have provided significant insights into the molecular mechanisms of these diseases. Nevertheless, data from different cohorts and pathologies are stored independently in public repositories and a unified resource is imperative to assist researchers in this field.

Midkine rewires the melanoma microenvironment toward a tolerogenic and immune-resistant state.

An open question in aggressive cancers such as melanoma is how malignant cells can shift the immune system to pro-tumorigenic functions. Here we identify midkine (MDK) as a melanoma-secreted driver of an inflamed, but immune evasive, microenvironment that defines poor patient prognosis and resistance to immune checkpoint blockade. Mechanistically, MDK was found to control the transcriptome of melanoma cells, allowing for coordinated activation of nuclear factor-κB and downregulation of interferon-associated pathways.

DREIMT: a drug repositioning database and prioritization tool for immunomodulation.

Motivation: Drug immunomodulation modifies the response of the immune system and can be therapeutically exploited in pathologies such as cancer and autoimmune diseases.

Results: DREIMT is a new hypothesis-generation web tool, which performs drug prioritization analysis for immunomodulation. DREIMT provides significant immunomodulatory drugs targeting up to 70 immune cells subtypes through a curated database that integrates 4960 drug profiles and ∼2600 immune gene expression signatures.

Cutaneous Immune Cell-Microbiota Interactions Are Controlled by Epidermal JunB/AP-1.

Atopic dermatitis (AD) is a multi-factorial skin disease with a complex inflammatory signature including type 2 and type 17 activation. Although colonization by S. aureus is common in AD, the mechanisms rendering an organism prone to dysbiosis, and the role of IL-17A in the control of S.

Oncogenic Rag GTPase signaling enhances B cell activation and drives follicular lymphoma sensitive to pharmacological inhibition of mTOR.

The humoral immune response demands that B cells undergo a sudden anabolic shift and high cellular nutrient levels which are required to sustain the subsequent proliferative burst. Follicular lymphoma (FL) originates from B cells that have participated in the humoral response, and 15% of FL samples harbor point, activating mutations in , an essential activator of mTORC1 downstream of the sensing of cellular nutrients. The impact of recurrent mutations in B cell function and lymphoma is unexplored.

Clonal dynamics monitoring during clinical evolution in chronic lymphocytic leukaemia.

Chronic lymphocytic leukaemia is the most prevalent leukaemia in Western countries. It is an incurable disease characterized by a highly variable clinical course. Chronic lymphocytic leukaemia is an ideal model for studying clonal heterogeneity and dynamics during cancer progression, response to therapy and/or relapse because the disease usually develops over several years.

PanDrugs: a novel method to prioritize anticancer drug treatments according to individual genomic data.

Background: Large-sequencing cancer genome projects have shown that tumors have thousands of molecular alterations and their frequency is highly heterogeneous. In such scenarios, physicians and oncologists routinely face lists of cancer genomic alterations where only a minority of them are relevant biomarkers to drive clinical decision-making. For this reason, the medical community agrees on the urgent need of methodologies to establish the relevance of tumor alterations, assisting in genomic profile interpretation, and, more importantly, to prioritize those that could be clinically actionable for cancer therapy.

Growth rate controls mRNA turnover in steady and non-steady states.

Gene expression has been investigated in relation with growth rate in the yeast Saccharomyces cerevisiae, following different experimental strategies. The expression of some specific gene functional categories increases or decreases with growth rate. Our recently published results have unveiled that these changes in mRNA concentration with growth depend on the relative alteration of mRNA synthesis and decay, and that, in addition to this gene-specific transcriptomic signature of growth, global mRNA turnover increases with growth rate.