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The development of reliable biomarkers for the prediction of immune checkpoint inhibition (ICI) response in patients with metastatic renal cell carcinoma (mRCC) and urothelial carcinoma (mUC) remains an unresolved challenge. Conventional ICI biomarkers typically focus on tumor-related factors such as PD-L1 expression. However, a comprehensive evaluation of the predictive value of serum electrolyte levels, a so far widely unexplored area, is still pending. We conducted a post-hoc analysis of baseline sodium, potassium, chloride, magnesium and calcium levels in two independent phase 3 clinical trials: IMvigor211 for mUC comparing atezolizumab to chemotherapy, and IMmotion151 for mRCC comparing atezolizumab+bevacizumab to sunitinib. This analysis aimed to evaluate the prognostic and predictive value of these electrolyte levels in these clinical settings. A total of 1787 patients (IMvigor211 n = 901; IMmotion151 n = 886) were analyzed. We found a linear correlation of baseline serum sodium and chloride with prognosis across both trials, which was not found for potassium, magnesium and calcium. In multivariate analysis, the prognostic capacity of sodium was limited to patients receiving ICI as compared to the control group. Interestingly, in both studies, the chance of achieving an objective response was highest in the patient subgroup with high baseline serum sodium levels of > 140 mmol/L (IMmotion151: Complete response in 17.9% versus 2.0% in patients with mRCC with baseline sodium < 135 mmol/L). Serum sodium outperformed tumor PD-L1 expression as a predictor for immunotherapy efficacy. Patients exhibiting elevated serum sodium levels derive the greatest benefit from immunotherapy, suggesting that baseline serum concentration could serve as a valuable and cost-effective predictive biomarker for immunotherapy across entities. • Sodium exhibits a linear correlation with survival in immunotherapy-treated patients • This correlation is not present for other serum electrolytes • The effect is significant in immunotherapy-treated patients only • High sodium identifies patients who profit from immunotherapy [ABSTRACT FROM AUTHOR]

About 40% of patients with non-small cell lung cancer (NSCLC) develop brain metastases (BMs) throughout the disease, and the occurrence of BMs is considered to have a fairly high mortality rate. Therefore, the management of brain metastases in NSCLC patients is a clinical challenge. Currently, multidisciplinary diagnosis and treatment methods are often used to achieve effective control of intracranial disease and prolong survival. Immunotherapy (IT) is one of the core therapies for NSCLC. Single or combined IT represented by immune checkpoint inhibitors(ICIs) of programmed death-1(PD-1)/ programmed cell death-ligand 1 (PD-L1) can significantly improve the prognosis of patients with advanced NSCLC.ICIs has been shown to be safe and effective in patients with BMs, although patients with BMs are mostly underrepresented in randomized clinical trials. In this review, we summarized the mechanism of ICIs in the treatment of BMs, and the clinical research and treatment progress of ICIs and their combination with other therapies in patients with BMs s from NSCLC. [ABSTRACT FROM AUTHOR]

Pembrolizumab has received approval as a first-line treatment for unresectable/metastatic triple-negative breast cancer (mTNBC) with a PD-L1 combined positive score (CPS) of ≥ 10. However, assessing CPS in mTNBC poses challenges. Firstly, it represents a novel analysis for breast pathologists. Secondly, the heterogeneity of PD-L1 expression in mTNBC further complicates the assessment. Lastly, the lack of standardized assays and staining platforms adds to the complexity. In KEYNOTE trials, PD-L1 expression was evaluated using the IHC 22C3 pharmDx kit as a companion diagnostic test. However, both the 22C3 pharmDx and VENTANA PD-L1 (SP263) assays are validated for CPS assessment. Consequently, assay-platform choice, staining conditions, and scoring methods can significantly impact the testing outcomes. This consensus paper aims to discuss the intricacies of PD-L1 CPS testing in mTNBC and provide practical recommendations for pathologists. Additionally, we present findings from a nationwide Italian survey elucidating the state-of-the-art in PD-L1 CPS testing in mTNBC. [Display omitted] • Breast pathologists face challenges in determining PD-L1 CPS score. • Lack of standardization across assays/staining platforms for PD-L1 CPS. • Validation and harmonization of the PD-L1 assays is crucial for consistent results. • Digital pathology may be of help, providing guidelines. • Infrastructures are present but challenges persist: harmonization, training. [ABSTRACT FROM AUTHOR]