Unusual Association of NF-κB Components in Tumor-Associated Macrophages (TAMs) Promotes HSPG2-Mediated Immune-Escaping Mechanism in Breast Cancer.

The cellular heterogeneity of the tumor environment of breast cancer (BC) is extremely complex and includes different actors such as neoplastic, stromal, and immunosuppressive cells, which contribute to the chemical and mechanical modification of the environment surrounding the tumor-exasperating immune-escaping mechanisms. In addition to molecular signals that make the tumor microenvironment (TME) unacceptable for the penetrance of the immune system, the physical properties of tumoral extracellular matrix (tECM) also have carved out a fundamental role in the processes of the protection of the tumor niche. Tumor-associated macrophages (TAMs), with an M2 immunosuppressive phenotype, are important determinants for the establishment of a tumor phenotype excluded from T cells. NF-κB transcription factors orchestrate innate immunity and represent the common thread between inflammation and cancer. Many studies have focused on canonical activation of NF-κB; however, activation of non-canonical signaling predicts poor survival and resistance to therapy. In this scenario, we demonstrated the existence of an unusual association of NF-κB components in TAMs that determines the deposition of HSPG2 that affects the stiffness of tECM. These results highlight a new mechanism counterbalanced between physical factors and a new perspective of mechano-pathology to be targeted to counteract immune evasion in BC.

Breast Reconstruction after Mastectomy with the Use of an Implant and Serratus Anterior Fascia Flap-Initial Clinical Evaluation.

Prosthesis-based techniques are the predominant form of breast reconstruction worldwide. The most performed surgical technique involves the placement of the expander in a partial submuscular plane. The coverage of the implant remains a difficult management problem that can lead to complications and poor outcomes. The use of the serratus fascia flap may be the best choice to create a subpectoral pocket for the placement of a tissue expander, with excellent results in terms of morbidity and cost-effectiveness. A total of 20 breast reconstructions with the inferolateral coverage with the serratus fascia were performed. Patients demonstrated a low overall complication rate (9.5%), such as seroma and infection, with complete resolution during the follow-up and no major complications. The US examination of the soft tissues over the implant reported thickness measurements that demonstrated a good coverage over the inferolateral area. Our study shows that using the serratus fascia flap to create a pocket with the pectoralis major for the placement of the tissue expander is an effective technique during two-stage breast reconstruction. The resulting low rate of morbidity and the US findings collected reveal the safety of this procedure. Its success relies on appropriate patient selection and specific intraoperative technique principles.