Longitudinal blood immune-inflammatory and radiomic profiling to decode different patterns of acquired resistance to immunotherapy in patients with NSCLC.

Purpose: To uncover the underpinnings of acquired resistance (AR) to immunotherapy (IO), we determined whether distinctive clinico-pathological, radiomic and peripheral blood (PB) immune-inflammatory features reflect oligo- and systemic (sys)-AR in advanced NSCLC patients undergoing immune checkpoints inhibitors.

Experimental Design: On 105 consecutive IO-treated advanced NSCLC, PB immunophenotypes, cytokines and CT-derived radiomic features (RFs), extracted from primary and merged metastatic lesions, were prospectively collected at baseline (T0) and first disease assessment (T1, 9-12 weeks), and their delta (Δ) variation [(T1-T0)/T0] computed. AR, defined as progression after initial response (complete/partial) or stable disease ≥ 6 months, was subdivided according to the number of new and/or progressive lesions in oligoAR (≤3) and sysAR (>3).

PD-L1 overexpression induces STAT signaling and promotes the secretion of pro-angiogenic cytokines in non-small cell lung cancer (NSCLC).

Background: Monoclonal antibodies (ICI) targeting the immune checkpoint PD-1/PD-L1 alone or in combination with chemotherapy have demonstrated relevant benefits and established new standards of care in first-line treatment for advanced non-oncogene addicted non-small cell lung cancer (NSCLC). However, a relevant percentage of NSCLC patients, even with high PD-L1 expression, did not respond to ICI, highlighting the presence of intracellular resistance mechanisms that could be dependent on high PD-L1 levels. The intracellular signaling induced by PD-L1 in tumor cells and their correlation with angiogenic signaling pathways are not yet fully elucidated.

Supraspinal neuroinflammation and anxio-depressive-like behaviors in young- and older- adult mice with osteoarthritis pain: the effect of morphine.

Rationale: Asteoarthritis (OA) is a leading cause of chronic pain in the elderly population and is often associated with emotional comorbidities such as anxiety and depression. Despite age is a risk factor for both OA and mood disorders, preclinical studies are mainly conducted in young adult animals.

Objectives: Here, using young adult (11-week-old) and older adult (20-month-old) mice, we evaluate in a monosodium-iodoacetate-(MIA)-induced OA model the development of anxio-depressive-like behaviors and whether brain neuroinflammation may underlie the observed changes.

Osteoarthritis Pain in Old Mice Aggravates Neuroinflammation and Frailty: The Positive Effect of Morphine Treatment.

Knee osteoarthritis is a common cause of pain and disability in old subjects. Pain may predispose to the development of frailty. Studies on mechanisms underlying pain in osteoarthritis models during aging are lacking.

Frailty and pain, human studies and animal models.

The hypothesis that pain can predispose to frailty development has been recently investigated in several clinical studies suggesting that frailty and pain may share some mechanisms. Both pain and frailty represent important clinical and social problems and both lack a successful treatment. This circumstance is mainly due to the absence of in-depth knowledge of their pathological mechanisms.