[Management of bone metastasis in non-small cell lung cancer].

Lung cancer is notoriously known for its predisposition to metastasize to the bones. Diagnostic tools, including positron emission tomography coupled with computed tomography, offer increased sensitivity in detecting bone infiltration. Management strategies encompass a multidisciplinary approach, including pharmacological pain management, anti-resorptive therapy, radiotherapy, interventional techniques, and surgery.

Neoantigen-specific CD8 T cells with high structural avidity preferentially reside in and eliminate tumors.

The success of cancer immunotherapy depends in part on the strength of antigen recognition by T cells. Here, we characterize the T cell receptor (TCR) functional (antigen sensitivity) and structural (monomeric pMHC-TCR off-rates) avidities of 371 CD8 T cell clones specific for neoantigens, tumor-associated antigens (TAAs) or viral antigens isolated from tumors or blood of patients and healthy donors. T cells from tumors exhibit stronger functional and structural avidity than their blood counterparts.

[Prostate cancer in the era of precision medicine: a new horizon].

Precision medicine is playing an increasingly crucial role in the treatment of prostate cancer. By tailoring treatments to the unique characteristics of patients and their tumors, this approach enables more targeted and personalized care, ultimately improving patient survival. In this article, we discuss the targeted therapies that have recently changed the management of this cancer.

[Oncology: what's new in 2022].

The past year has brought several innovations in medical oncology, opening up promising new options for many solid tumors, both localized and metastatic. Immunotherapy, a real spearhead of emerging therapies in metastatic diseases, is seeing its use extend to adjuvant and neoadjuvant modalities, particularly in colon and lung cancers. 2022 also sees a great deal of focus on targeted therapies, as well as on antibody-drug conjugates, which creates new standards in both breast and lung cancers.

Salvage LATTICE radiotherapy for a growing tumour despite conventional radio chemotherapy treatment of lung cancer.

A 40-year-old patient with cT4cN1M0 squamous cell lung cancer of the upper right lobe received preoperative induction chemotherapy. Systemic induction treatment failed to reverse tumour growth with the addition of conventional radiotherapy (RT). A salvage lattice RT boost of 12 Gy was administered immediately to increase the dose to the tumour.

[Targeted therapies and non-small cell carcinomas : novelties].

In recent years, new therapeutic strategies for non-small cell lung cancer (NSCLC) have been developed, stemming from a better understanding of oncogenic signaling pathways. The analysis of the alterations of genes involved in NSCLC oncogenesis is now an integral part of the diagnostic approach and opens the way to so-called "targeted" therapies. In this article, we will share the latest therapeutic advances by focusing on alterations of HER2, MET, EGFR and KRAS genes, for which new dedicated treatments have become available.

Sensitive identification of neoantigens and cognate TCRs in human solid tumors.

The identification of patient-specific tumor antigens is complicated by the low frequency of T cells specific for each tumor antigen. Here we describe NeoScreen, a method that enables the sensitive identification of rare tumor (neo)antigens and of cognate T cell receptors (TCRs) expressed by tumor-infiltrating lymphocytes. T cells transduced with tumor antigen-specific TCRs identified by NeoScreen mediate regression of established tumors in patient-derived xenograft mice.

Development of an optimized closed and semi-automatic protocol for Good Manufacturing Practice manufacturing of tumor-infiltrating lymphocytes in a hospital environment.

Background Aims: Several studies report on Good Manufacturing Process (GMP)-compliant manufacturing protocols for the ex vivo expansion of tumor-infiltrating lymphocytes (TILs) for the treatment of patients with refractory melanoma and other solid malignancies. Further opportunities for improvements in terms of ergonomy and operating time have been identified.

Methods: To enable GMP-compliant TILs production for adoptive cell therapy needs, a simple automated and reproducible protocol for TILs manufacturing with the use of a closed system was developed and implemented at the authors' institution.

Personalized Cytokine-Directed Therapy With Tocilizumab for Refractory Immune Checkpoint Inhibitor-Related Cholangiohepatitis.

Introduction: For patients with corticosteroid (CS)-refractory immune checkpoint inhibitor-related cholangiohepatitis (irCH), no consensus exists regarding treatment, and outcomes remain poor. We evaluated the possibility of personalized treatment according to the patient's cytokine profile and the immunohistopathologic assessment of the predominant immune infiltrate type of liver tissue.

Methods: NSCLCs with CS-refractory irCH were analyzed by immunohistochemistry of liver biopsy specimen, serum cytokine panel, and assessment of peripheral blood mononuclear cell immune cell monitoring by mass cytometry.

[Small-cell lung cancer: management and novelties].

Small cell lung cancer is a recalcitrant malignancy with 5-year survival rates of less than 20%. In the majority of cases, patients have metastatic disease at diagnosis despite the new screening method by low-dose CT-scan. The high throughput sequencing has deepened our understanding of its biology.

[Surgical treatment of proximal femur metastases].

Aging of the population results in an increase of the incidence of cancer and bone metastases. The proximal femur is one of the most frequent locations of bone metastases. A pathological fracture has a major impact on the quality of life and potentially on survival.

Adenosine mediates functional and metabolic suppression of peripheral and tumor-infiltrating CD8 T cells.

Background: Several mechanisms are present in the tumor microenvironment (TME) to impair cytotoxic T cell responses potentially able to control tumor growth. Among these, the accumulation of adenosine (Ado) contributes to tumor progression and represents a promising immunotherapeutic target. Ado has been shown to impair T cell effector function, but the role and mechanisms employed by Ado/Ado receptors (AdoRs) in modulating human peripheral and tumor-infiltrating lymphocyte (TIL) function are still puzzling.

[The new management options for lung cancer in the immunotherapy era].

Lung cancer is the leading cause of cancer related deaths worldwide. Since the advent of immunotherapy, survival has significantly improved. Though encouraging treatment results, initially only some patients used to benefit significantly and specifically from immunotherapy administered alone.

BRAF Alterations as Therapeutic Targets in Non-Small-Cell Lung Cancer.

Background: Several subsets of non-small-cell lung cancer (NSCLC) are defined by molecular alterations acting as tumor drivers, some of them being currently therapeutically actionable. The rat sarcoma (RAS)-rapidly accelerated fibrosarcoma (RAF)-mitogen-activated protein/extracellular signal-regulated kinase kinase (MEK)-extracellular signal-regulated kinase (ERK) pathway constitutes an attractive potential target, as v-Raf murine sarcoma viral oncogene homolog B (BRAF) mutations occur in 2-4% of NSCLC adenocarcinoma.

Methods: Here, we review the latest clinical data on BRAF serine/threonine kinase inhibitors in NSCLC.

Reinvention of chemotherapy: drug conjugates and nanoparticles.

Purpose Of Review: Recent advances in nanotechnology have addressed some of the issues related to lack of selectivity and nonspecific toxicities associated with conventional chemotherapy. Nanoparticles are therapeutic carriers that can be fine tuned for specific application and for passive or active tumor targeting.

Recent Findings: Although the nanoparticle field is rapidly expanding, there are to date only six nanoparticle-based drug delivery platforms and two antibody-drug conjugates that are clinically approved for cancer therapy.

NuMA-related LIN-5, ASPM-1, calmodulin and dynein promote meiotic spindle rotation independently of cortical LIN-5/GPR/Galpha.

The spindle apparatus dictates the plane of cell cleavage, which is critical in the choice between symmetric or asymmetric division. Spindle positioning is controlled by an evolutionarily conserved pathway, which involves LIN-5/GPR-1/2/Galpha in Caenorhabditis elegans, Mud/Pins/Galpha in Drosophila and NuMA/LGN/Galpha in humans. GPR-1/2 and Galpha localize LIN-5 to the cell cortex, which engages dynein and controls the cleavage plane during early mitotic divisions in C.

Coupling of cortical dynein and G alpha proteins mediates spindle positioning in Caenorhabditis elegans.

Despite being essential for spatial cell division control, the mechanisms governing spindle positioning remain incompletely understood. In the Caenorhabditis elegans one-cell stage embryo, the spindle becomes asymmetrically positioned during anaphase through the action of as-yet unidentified cortical force generators that pull on astral microtubules and that depend on two G alpha proteins and associated proteins. We performed spindle-severing experiments following temporally restricted gene inactivation and drug exposure, and established that microtubule dynamics and dynein are both required for generating efficient pulling forces.

PchR-box recognition by the AraC-type regulator PchR of Pseudomonas aeruginosa requires the siderophore pyochelin as an effector.

Under iron limitation, the opportunistic human pathogen Pseudomonas aeruginosa produces the siderophore pyochelin. When secreted into the extracellular environment, pyochelin complexes ferric ions and delivers them, via the outer membrane receptor FptA, to the bacterial cytoplasm. Extracellular pyochelin also acts as a signalling molecule, inducing the expression of pyochelin biosynthesis and uptake genes by a mechanism involving the AraC-type regulator PchR.