CAR-Based Strategies beyond T Lymphocytes: Integrative Opportunities for Cancer Adoptive Immunotherapy.

Chimeric antigen receptor (CAR)-engineered T lymphocytes (CAR Ts) produced impressive clinical results against selected hematological malignancies, but the extension of CAR T cell therapy to the challenging field of solid tumors has not, so far, replicated similar clinical outcomes. Many efforts are currently dedicated to improve the efficacy and safety of CAR-based adoptive immunotherapies, including application against solid tumors. A promising approach is CAR engineering of immune effectors different from αßT lymphocytes. Herein we reviewed biological features, therapeutic potential, and safety of alternative effectors to conventional CAR T cells: γδT, natural killer (NK), NKT, or cytokine-induced killer (CIK) cells. The intrinsic CAR-independent antitumor activities, safety profile, and ex vivo expansibility of these alternative immune effectors may favorably contribute to the clinical development of CAR strategies. The proper biological features of innate immune response effectors may represent an added value in tumor settings with heterogeneous CAR target expression, limiting the risk of tumor clonal escape. All these properties bring out CAR engineering of alternative immune effectors as a promising integrative option to be explored in future clinical studies.

Biomechanical and biochemical assessment of YB-1 expression in A375 melanoma cell line: Exploratory study.

Malignant melanoma is the most lethal form of skin cancer. Y-box binding protein 1 (YB-1) plays a prominent role in mediating metastatic behavior by promoting epithelial-to-mesenchymal transition (EMT). Migratory melanoma cells exhibit two major migration modes: elongated mesenchymal or rounded amoeboid. Using A375 melanoma cell line and the YB-1 knock-out model, we aimed to elucidate biochemical and biomechanical changes in migration signaling pathways in the context of melanoma metastases. We subjected A375 YB-1 knock-out and parental cells to atomic force microscopy (stiffness determination), immunolabelling, and proteome analysis. We found that YB-1 expressing cells were significantly stiffer compared to the corresponding YB-1 knock-out cell line. Our study demonstrated that the constitutive expression of YB-1 in A375 melanoma cell line appears to be closely related to known biomarkers of epithelial-to-mesenchymal transition, nestin, and vimentin, resulting in a stiffer phenotype, as well as a wide array of proteins involved in RNA, ribosomes, and spliceosomes. YB-1 knock-out resulted in nestin depletion and significantly lower vimentin expression, as well as global upregulation of proteins related to the cytoskeleton and migration. YB-1 knock-out cells demonstrated both morphological features and biochemical drivers of mesenchymal/ameboid migration. Melanoma is a highly plastic, adaptable, and aggressive tumor entity, capable of exhibiting characteristics of different migratory modes.

Detecting early osteoarthritis through changes in biomechanical properties - A review of recent advances in indentation technologies in a clinical arthroscopic setup.

Osteoarthritis (OA) is a degenerative joint disease currently affecting half of all women and one-third of all men aged over 65 and it is predicted to even increase in the next decades. In the variety of causes leading to OA, the first common denominator are changes in the extracellular matrix of the cartilage. In later stages, OA affects the whole joint spreading to higher levels of tissue architecture causing irreversible functional and structural damage. To date, the diagnosis of OA is only formulated in the late stages of the disease. This is also, where most present therapies apply. Since a precise diagnosis is a prerequisite for targeted therapy, tools to diagnose early OA, monitor its progression, and accurately stage the disease are wanted. This review article focuses on recent advances in indentation technologies to diagnose early OA through describing biomechanical cartilage characteristics. We provide an overview of microindentation instruments, indentation-type Atomic Force Microscopy, ultrasound, and water-jet ultrasound indentation, Optical Coherence Tomography-based air-jet indentation, as well as fiber Bragg grating.

Assessment of 5-Aminolevulinic Acid-Mediated Photodynamic Therapy on Bone Metastases: An in Vitro Study.

Bone is a frequent site of metastases, being typically associated with a short-term prognosis in affected patients. Photodynamic therapy (PDT) emerges as a promising alternative treatment for controlling malignant disease that can directly target interstitial metastatic lesions. The aim of this study was to assess the effect induced by PDT treatment on both primary (giant cell bone tumor) and human bone metastatic cancer cell lines (derived from a primary invasive ductal breast carcinoma and renal carcinoma). After 24 h post light delivery (blue light-wavelength 436 nm) with 5-aminolevulinic acid, the effect on cellular migration, viability, apoptosis, and senescence were assessed. Our results showed that bone metastasis derived from breast cancer reacted with an inhibition of cell migration coupled with reduced viability and signs of apoptosis such as nuclei fragmentation following PDT exposure. A limited effect in terms of cellular viability inhibition was observed for the cells of giant cell bone tumors. In contrast, bone metastasis derived from renal carcinoma followed a different fate-cells were characterized by senescent features, without a notable effect on cell migration or viability. Collectively, our study illustrates that PDT could act as a successful therapy concept for local tumor control in some entities of bone metastases.

New technologies in breast cancer sentinel lymph node biopsy; from the current gold standard to artificial intelligence.

Sentinel lymph node biopsy is an important diagnostic procedure performed in early breast cancer patients with clinically negative axillary lymph nodes. Detection and examination of sentinel lymph nodes determine further therapy decisions, therefore a choice of optimal technique minimising the risk of false-negative results is of great importance. Currently, the gold standard is the dual technique comprising the blue dye and radiotracer, however, this method creates a logistical problem for many medical units. The intrinsic constraints of the existing methods led to the development of a very wide range of alternatives with varying clinical efficiency and feasibility. While each method presents with its own advantages and disadvantages, many techniques have improved enough to become a non-inferior alternative in the sentinel lymph node biopsy. Along with the improvement of the existing technologies, there are evolving trends such as multimodality of the techniques maximising the diagnostic outcome or an emerging use of artificial intelligence (AI) improving the workflow of the procedure. This literature review aims to give an overview of the current status of the standard techniques and emerging cutting-edge technologies in the sentinel lymph node biopsy.