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Natural Killer (NK) cells are integral to the innate immune system, renowned for their ability to target and eliminate cancer cells without the need for antigen presentation, sparing normal tissues. These cells are crucial in cancer immunosurveillance due to their diverse array of activating and inhibitory receptors that modulate their cytotoxic activity. However, the tumor microenvironment can suppress NK cell function through various mechanisms. Over recent decades, research has focused on overcoming these tumor escape mechanisms. Initially, efforts concentrated on enhancing T cell activity, leading to impressive results with immunotherapeutic approaches aimed at boosting T cell responses. Nevertheless, a substantial number of patients do not benefit from these treatments and continue to seek effective alternatives. In this context, NK cells present a promising avenue for developing new treatments, given their potent cytotoxic capabilities, safety profile, and activity against T cell-resistant tumors, such as those lacking HLA-I expression. Recent advancements in immunotherapy include strategies to restore and amplify NK cell activity through immune checkpoint inhibitors, cytokines, adoptive NK cell therapy, and CAR-NK cell technology. This review provides a comprehensive overview of NK cell receptors, the tumor escape mechanisms that hinder NK cell function, and the evolving field of NK cell-based cancer immunotherapy, highlighting ongoing efforts to develop more effective and targeted cancer treatment strategies., Competing Interests: Declaration of competing interest Federica Papaccio: private institutional research funding from Merck, travel support from Diatech Pharmacogenetics, ESMO Translational Research Fellowship sponsored by Amgen from 2018 to 2020. The other authors declare no conflicts of interest., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

This review focuses on the immune checkpoint inhibitors (ICIs) in the context of breast cancer (BC) management. These innovative treatments, by targeting proteins expressed on both tumor and immune cells, aim to overcome tumor-induced immune suppression and reactivate the immune system. The potential of this approach is the subject of numerous clinical studies. Here, we explore the key studies and emerging therapies related to ICIs providing a detailed analysis of their specific and combined use in BC treatment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

We examined the conformation of benzo-15-crown-5 (B15C5) and benzo-18-crown-6 (B18C6) complexes with ammonium ions, NH 4 + , CH 3 NH 3 + (MeNH 3 + ), CH 3 CH 2 NH 3 + (EtNH 3 + ), and CH 3 CH 2 CH 2 NH 3 + (PrNH 3 + ), using cold UV and IR spectroscopy in the gas phase. We measured the UV photodissociation (UVPD) spectra of the ammonium complexes and compared them with those of the K + (B15C5) and K + (B18C6) complexes in order to identify the conformation on the basis of the band position. The number of possible conformations for the ammonium complexes of B15C5 is limited compared with alkali metal ions with similar ionic radii. The NH 4 + (B15C5), MeNH 3 + (B15C5), and EtNH 3 + (B15C5) complexes show two conformers, whereas the K + (B15C5) complex has three stable conformers. In the case of the PrNH 3 + (B15C5) complex, one conformer was found predominantly in the UVPD spectrum. The ammonium complexes of B15C5 prefer to adopt crown conformations with large dihedral angles on the C-O-C-C atoms around the benzene moiety. In the case of the ammonium complexes of B18C6, two or three conformers were found in the UVPD spectra. One conformation of the B18C6 complexes is similar to that of the K + (B18C6) complex, which has a planar form on the C-O-C-C atoms around the benzene moiety. The other but dominant conformations of the ammonium complexes could be attributed to those with large C-O-C-C dihedral angles. These conformational findings for the ammonium complexes suggest that the benzo-crown ethers tend to adopt nonplanar conformations around the benzene moiety to encapsulate the ammonium ions. The IR-UV double-resonance (DR) spectra of the B15C5 and B18C6 complexes were compared to those of benzo-12-crown-4 (B12C4) and dibenzo-18-crown-6 (DB18C6) complexes. The N-H···O hydrogen bond (H-bond) is weaker with increasing ring size from B12C4 to B18C6, although the calculated binding energy is smaller for B12C4 than for B18C6. This result indicates that cooperative H-bonds with three N-H groups can strengthen the intermolecular bond between the ammonium ions and B18C6. The difference in the conformational preference between the ammonium and K + complexes is attributed to directed N-H···O H-bonds in the ammonium complexes. Proton transfer and dissociation of the crown ring were also observed for the photoexcitation of the NH 4 + (B15C5) and NH 4 + (B18C6) complexes.

Validation of biomarker assays is crucial for effective drug development and clinical applications. Interlaboratory reproducibility is vital for reliable comparison and combination of data from different centers. This review summarizes interlaboratory studies of quantitative LC-MS-based biomarker assays using reference standards for calibration curves. The following points are discussed: trends in reports, reference and internal standards, evaluation of analytical validation parameters, study sample analysis and normalization of biomarker assay data. Full evaluation of these parameters in interlaboratory studies is limited, necessitating further research. Some reports suggest methods to address variations in biomarker assay data among laboratories, facilitating organized studies and data combination. Method validation across laboratories is crucial for reducing interlaboratory differences and reflecting target biomarker responses.