Case report: A case of acute mastitis associated with reactive cutaneous capillary endothelial proliferation after camrelizumab treatment: A new immune-related adverse event.

Lung cancer is a malignant tumor with the highest morbidity and mortality rate worldwide, and it seriously endangers human health. In recent years, immunotherapy has been widely used in lung cancer and has achieved great benefits, especially the application of promoting antitumor immune defense. However, immune-related adverse events (irAEs) caused by immune checkpoint inhibitors have received increasing attention, which largely limits their use. We report the first case of new acute mastitis caused by anti-PD1 inhibitors due to lung adenocarcinoma. A 65-year-old female patient came to our hospital for treatment with cough and shortness of breath for one month. Chest CT showed that the malignant tumor in the lower lobe of the right lung with pleural effusion had metastasized to many places, and then pleural effusion was taken for pathological examination. Pathological examination indicated that the pleural fluid originated from lung adenocarcinoma. Subsequently, the patient received platinum-containing dual-agent chemotherapy (carboplatin and pemetrexed disodium) combined with immunotherapy (camrelizumab). During treatment, the patient developed known adverse events and unreported acute mastitis. After stopping camrelizumab, the patient's mastitis gradually improved. Our case shows that acute mastitis might be a new adverse event after the use of camrelizumab. Since this new adverse event has not been reported, we hope that oncology medical workers can obtain insight from our case and use it as a reference for the identification and management of irAEs.

Case Report: Upper limb dysfunction may be caused by chest wall mass excision: An enlightenment from a special case.

Of all the thoracic surgical procedures, chest wall surgery is probably the lowest-risk type. In fact, it is not so. Clinical work also often has the trap of chest wall surgery. An operation to remove a mass in the axilla may result in upper limb disability on the affected side. Here, we report the case of a 47-year-old female patient with a left chest wall adjacent axillary mass, which was considered an abnormal structural lymph node on color ultrasound examination and chest CT. Otherwise, she felt no discomfort. The left upper limb moved freely without being affected by the mass. A routine resection of the tumor was performed after the preoperative examination was completed. After the operation, the incision recovered well. However, the day after the surgery, she developed numbness and pain in her left little finger and ring finger, pain that often kept her from sleeping. The mass was confirmed to be a schwannoma with cystic degeneration by pathology slicing after the operation. By this time, doctors were alerted to the fact that the removal of the chest wall mass had nearly disabled the left upper limb of the patient, which was a great warning to the thoracic surgeon. In this case report, we hope that all surgeons will be cautious and careful and will not trust the imaging diagnosis too much. It is also hoped that the patient understands that some procedures may lead to unexpected complications.

Down-regulation of MLLT1 super elongation complex subunit impairs the anti-tumor activity of natural killer cells in esophageal cancer.

Natural killer (NK) cells actively participate in anti-tumor immunity and are thus regarded as a promising tool in immunotherapy against esophageal cancer (EC). However, the mechanisms regulating NK cell activation and exhaustion have not been completely elucidated. In this study, we characterized the expression and function of MLLT1 super elongation complex subunit (MLLT1) in esophageal NK cells in a mouse EC model. MLLT1 was down-regulated in esophageal NK cells, especially NK cells expressing both T cell immunoglobulin and mucin-domain containing-3 (TIM-3) and lymphocyte activation gene3(LAG-3). In vitro knockdown of MLLT1 in NK cells resulted in significant decreases in the expression of IFN-γ and perforin, as well as impaired NK cell cytotoxicity on tumor cells. Adoptive transfer of MLLT-deficient NK cells into EC-bearing mice showed consistent impairment of NK cell anti-tumor activity, as evidenced by decreases in IFN-γ and perforin but not granzyme B. Furthermore, EC tissue cells, which were enriched from the esophagus of EC-bearing mice, induced down-regulation of MLLT1 in splenic NK cells. This down-regulation was partially restored by a TIM-3 blocking antibody. Therefore, this study indicated that TIM-3 signaling down-regulated MLLT1 in esophageal NK cells, and MLLT1 down-regulation undermined the tumoricidal function of NK cells in EC. Our study unveils a novel mechanism underlying NK cell exhaustion/dysfunction in the EC microenvironment. MLLT1 could be a potential target in future NK cell-mediated immunotherapy against EC.

Interleukin-6 receptor alpha and CD27 discriminate intratumoral T helper 17 subpopulations with distinct functional properties in a mouse lung cancer model.

BACKGROUND: T helper 17 (Th17) cells actively participate in the tumor immune response in lung cancer. However, the heterogeneity and plasticity of intratumoral Th17 cells in lung cancer remain elusive. In this study, Th17 subpopulations were characterized in a mouse lung cancer model. METHODS: Urethane was administered to induce lung cancer in interleukin (IL)-17-EGFP transgenic mice. Flow cytometry was used to analyze the phenotypes, signaling status, and functions of Th17 subpopulations either in vivo or in vitro. The adoptive transfer assay and real-time polymerase chain reaction were applied to analyze the plasticity of Th17 subpopulations. RESULTS: IL-6Rαhigh CD27- Th17 and IL-6Rαlow CD27+ Th17 were identified in intratumoral Th17 cells. The two subpopulations expressed equivalent RORγt. However, the former expressed higher T-bet but lower Foxp3, more IL-17A and IFN-γ but less IL-10 than the latter. Furthermore, IL-6Rαhigh CD27- Th17 moderately inhibited the proliferation of lung cancer cells while IL-6Rαlow CD27+ Th17 could not. IL-6Rαhigh CD27- Th17 exhibited weaker Jun N-terminal kinases (JNK) signaling but stronger signal transducer and activator of transcription 3 (Stat3) signaling than IL-6Rαlow CD27+ Th17. The adoptive transfer assay indicated that both subpopulations downregulated RORγt in recipients' spleens but maintained RORγt in recipients' lungs. Meanwhile, IL-6Rαhigh CD27- Th17 expressed higher T-bet and IFN-γ than IL-6Rαlow CD27+ Th17 in the recipients. IL-6Rαlow CD27+ Th17 expressed Foxp3 and IL-10 in recipients' spleens but not lungs. CONCLUSIONS: This study reveals intratumoral Th17 subpopulations with distinct functional properties and signaling patterns, thus offering valuable insight into Th17 heterogeneity and plasticity in lung cancer.