Head and neck squamous cell carcinomas (HNSCCs) are an aggressive, genetically complex and difficult to treat group of cancers. In lieu of truly effective targeted therapies, surgery and radiotherapy represent the primary treatment options for most patients. But these treatments are associated with significant morbidity and a reduction in quality of life. Resistance to both radiotherapy and the only available targeted therapy, and subsequent relapse are common. Research has therefore focussed on identifying biomarkers to stratify patients into clinically meaningful groups and to develop more effective targeted therapies. However, as we are now discovering, the poor response to therapy and aggressive nature of HNSCCs is not only affected by the complex alterations in intracellular signalling pathways but is also heavily influenced by the behaviour of the extracellular microenvironment. The HNSCC tumour landscape is an environment permissive of these tumours' aggressive nature, fostered by the actions of the immune system, the response to tumour hypoxia and the influence of the microbiome. Solving these challenges now rests on expanding our knowledge of these areas, in parallel with a greater understanding of the molecular biology of HNSCC subtypes. This update aims to build on our earlier 2014 review by bringing up to date our understanding of the molecular biology of HNSCCs and provide insights into areas of ongoing research and perspectives for the future.

/pdf/clinical-update-on-head-and-neck-cancer-molecular-biology-52eo4oyczp.pdf

Clinical update on head and neck cancer: molecular biology and ongoing challenges.

Antitumor effects of immunity-enhancing traditional Chinese medicine.

Primary mediastinal B-cell lymphoma (PMBCL) is a distinct disease closely related to classical nodular sclerosing Hodgkin lymphoma. Conventional diagnostic paradigms utilising clinical, morphological and immunophenotypical features can be challenging due to overlapping features with other B-cell lymphomas. Reliable diagnostic and prognostic biomarkers that are applicable to the conventional diagnostic laboratory are largely lacking. Nuclear factor kappa B (NF-κB) and Janus kinase/signal transducers and activators of transcription (JAK-STAT) signalling pathways are characteristically dysregulated in PMBCL and implicated in several aspects of disease pathogenesis, and the latter pathway in host immune evasion. The tumour microenvironment is manipulated by PMBCL tumours to avoid T-cell mediated destruction via strategies that include loss of tumour cell antigenicity, T-cell exhaustion and activation of suppressive T-regulatory cells. R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone) and DA-EPOCH-R (dose-adjusted etoposide, prednisolone, vincristine, cyclophosphamide, doxorubicin, rituximab) are the most common first-line immunochemotherapy regimens. End of treatment positron emission tomography scans are the recommended imaging modality and are being evaluated to stratify patients for radiotherapy. Relapsed/refractory disease has a relatively poor outcome despite salvage immunochemotherapy and subsequent autologous stem cell transplantation. Novel therapies are therefore being developed for treatment-resistant disease, targeting aberrant cellular signalling and immune evasion.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/bjh.15778

Biology and Therapy of Primary Mediastinal B-cell Lymphoma: Current Status and Future Directions

Reprogramming the T cell response to cancer by simultaneous, nanoparticle-mediated PD-L1 inhibition and immunogenic cell death

Recent advances in nanosized drug delivery systems for overcoming the barriers to anti-PD immunotherapy of cancer

Tumor cells can evade immune surveillance through overexpressing the ligands of checkpoint receptors on tumor cells or adjacent cells, leading T cells to anergy or exhaustion. Growing evidence of the interaction between tumor cells and microenvironment promoted the emergence of immune-checkpoint blockade. By targeting programmed cell death-1 (PD-1) pathway, cytotoxic activity of T cell is enhanced significantly and tumor cell lysis is induced subsequently. Currently, various antibodies against PD-1 and programmed death-ligand 1 (PD-L1) are under clinical studies in lymphomas. In this review, we outline the rationale for investigation of PD-1-PD-L1 immune-checkpoint blockade in lymphomas and discuss their prospect of applications in clinical treatment.

PD-1-PD-L1 immune-checkpoint blockade in malignant lymphomas

Splenic marginal zone lymphoma (SMZL) is an uncommon indolent B-cell non-Hodgkin's lymphoma. The clinical features of SMZL are splenomegaly, lymphocytosis and cytopenia in peripheral blood. Immunopheno-typically, the neoplastic cells are typically positive for CD45, CD20, CD79a, PAX5, IgD, BCL-2. The previous common used treatment is splenectomy and chemotherapy. Nowadays, rituximab-based chemotherapy regimens has improved the curative effect dramaticlly. IFN-α with or without ribavirin can be used to treat the patients with HCV infection. Some new target agents such as Bruton tyrosine kinase, NOTCH inhibitor, CAL-101 are under clinical research. This review mainly discuss the progress in the treatment of SMZL.

[Progress on Treatment of Splenic Marginal Zone Lymphoma-Review].

Multiple myeloma (MM) is a hematological neoplasm which results in diffuse or focal bone infiltration and extramedullary lesions. It’s reported that infiltration of organs by plasma cells indicated worse prognosis, but the prognosis of patients with bone-related extramedullary disease (bEMD) is still unknown. One hundred and fourteen newly diagnosed MM patients were retrospectively reviewed. Results showed that the clinical features, overall survival (OS), and progression-free survival (PFS) of patients with and without bEMD had no statistical significance. Rib (46.1%) and vertebrae (17.9%) are common sites bEMD involved. Patients with diffuse bEMD had worse prognosis compared with patients with focal bEMD. Bisphosphonates played an important role in prolonging the survival of patients with bEMD. Positron emission tomography (PET)/computed tomography (CT) is sensitive in discovering bEMD than whole body low dose CT suggesting PET/CT to be a promising technique for initial staging. High β2-microglobulin and low albumin indicated shorter survival in patients with bEMD.

/pdf/clinical-characteristics-and-prognosis-of-multiple-myeloma-1hu9m5m0o1.pdf

Clinical characteristics and prognosis of multiple myeloma with bone-related extramedullary disease at diagnosis

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PD-1-PD-L1 immune-checkpoint blockade in malignant lymphomas

[Progress on Treatment of Splenic Marginal Zone Lymphoma-Review].

Clinical characteristics and prognosis of multiple myeloma with bone-related extramedullary disease at diagnosis