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Pulmonary large-cell neuroendocrine carcinoma (LCNEC) is a rare and highly aggressive cancer with a very poor prognosis. The proper treatment decision and possible prognosis outcome for advanced LCNEC is always an enormous challenge due to its scarcity. Here, we presented a 59-year-old male patient with advanced LCNEC with a non-neuroendocrine immunophenotype who received endostar plus pembrolizumab combined with a platinum-based dual chemotherapy regime as a first-line treatment. At present, the patient’s condition is well controlled by medication only and has a progression-free survival of more than 2 years. Adverse effects recorded for this patient during treatment courses include nausea, vomiting, II–III quality bone marrow toxicity, and PD-1 blockage-related hypothyroidism. This case report discussed the feasibility of immunotherapy, anti-angiogenesis agents, and chemotherapy as a first-line therapy in advanced LCNEC.

Lung cancer is the leading cause of cancer-related deaths across the world, of which non-small cell lung cancer (NSCLC) accounts for 85%, and more than 50% of NSCLC patients were diagnosed with distant metastasis. The comprehensive treatment of NSCLC includes surgery, radiotherapy, chemotherapy, targeted therapy and immune checkpoint inhibitors. As one of the traditional treatment methods, radiotherapy plays an important role in the treatment of all stages of NSCLC, and its immunomodulatory effect has attracted much attention. The application of immune checkpoint inhibitors (ICIs) has significantly improved the prognosis of patients with local-advanced and advanced NSCLC, but the benefit population was limited. At present, the treatment mode of radiotherapy combined with ICIs has become the focus of research. This paper reviews the research progress of radiotherapy combined with ICIs in the treatment of NSCLC.

Background: Programmed cell death protein 1 (PD-1) antibody has been approved for a variety of tumors, but its effective rate is unsatisfactory. New evidence suggests that mast cells are an important component of the tumor microenvironment and are associated with resistance to immunotherapy, but the underlying mechanism is not clear. Methods: Bioinformatics analysis of patients with melanoma in TCGA-SKCM and GSE91061 was used to determine the prognostic value of mast cells and their association with anti-PD-1 immunotherapy. HMC-1 cells (mast cell line) and bone marrow-derived mast cells (BMMCs) were used to verify the effect of PD-1 antibody and cromolyn sodium in vitro. The mouse subcutaneous melanoma model was used to verify the effect of the PD-1 antibody on mast cells in vivo. Results: Bioinformatics analysis showed that mast cells were a poor prognostic factor associated with resistance to anti-PD-1 immunotherapy. PD-1 was expressed on the mast cell membrane. The PD-1 antibody promoted the release of histamine and cytokines from mast cells via the PI3K/AKT pathway and calcium signaling pathway. The activation of mast cells induced by PD-1 antibody could be partially inhibited by cromolyn sodium. In vivo, cromolyn sodium increased the efficacy of PD-1 antibody and decreased the infiltration of mast cells and the density of microvessels. Conclusion: PD-1+ mast cell activated by PD-1 antibody plays a negative role in the tumor microenvironment via the enhanced function of releasing histamine and cytokines. Inhibition of mast cell may provide a new solution to solve the low response rate of anti-PD-1 immunotherapy. [ABSTRACT FROM AUTHOR]

Vesicles, also known as "microparticles", are vesicle‐like structures that are released outside the cell in a "sprouting" manner when the cytoskeleton is changed during cell activation or apoptosis, with a diameter of about 100–1000 nm, and are carriers of material information exchange between cells. Tumor‐derived extracellular vesicles can effectively deliver drugs to the nucleus of tumor stem cells, thus effectively killing them without toxic side effects. The underlying mechanism involves the soft nature of tumor stem cells that allows better uptake of vesicles, and the entry of drug‐carrying vesicles into lysosomes and facilitation of lysosomal movement toward the nucleus to deliver drugs to the nucleus. Drug‐loaded vesicles have unique advantages, such as low immunogenicity, homing targeting ability, and the ability to break through the physiological barrier to tumor therapy. Tumor‐derived drug‐delivery vesicles have entered clinical trials for the treatment of malignant pleural effusions. In this review, we summarized the progress of basic and clinical research on tumor cell‐derived drug‐loaded vesicles for the treatment of malignant pleural effusion in recent years. [ABSTRACT FROM AUTHOR]

Purpose: Our purpose was to explore which immobilization is more suitable for clinical practice in postmastectomy intensity modulation radiotherapy, the single‐pole position or the double‐pole position? Methods: Patients treated with postmastectomy intensity modulation radiotherapy were eligible. They were selected randomly for single‐pole position or double‐pole position. Dose–volume histogram (DVH) was used to evaluate plans. After their first radiotherapy, the physicians asked a question about the comfort level of their position. The dosimetric parameters, comfort levels, and reproducibility of the two immobilization techniques were collected and analyzed after all patients had finished the whole radiotherapy. Results: Totally, 94 patients were enrolled. Of these, 54 patients were treated with the single‐pole position, 28 (51.9%)had left‐sided lesions. While 40 patients were treated with the double‐pole position, 20 (50%) had left‐sided lesions. Patients' characteristics in two groups were comparable. The single‐pole and double‐pole immobilizations had similar conformity (0.60 ± 0.05 vs 0.60 ± 0.06, P = 0.887) and homogeneity index (0.14 ± 0.03 vs 0.13 ± 0.03, P = 0.407). Compared to single‐pole position, double‐pole position typically increased the mean dose, V20, and V30 of heart (P < 0.05). Moreover, patients in the single‐pole group felt more comfortable than another group (P < 0.05). There was no difference in reproducibility between the two groups (P > 0.05). Conclusions: Single‐pole position seems to be more comfortable and can reduce dose coverage to heart. Both devices allow for reproducible setup and acceptable dosimetry. [ABSTRACT FROM AUTHOR]