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Leptomeningeal metastasis (LM) is a complication of non-small cell lung cancer (NSCLC) characterized by poor prognosis and short survival. A variety of therapeutic approaches have been sought to improve the efficacy of LM. Here we present a clinical case and conduct a literature review to investigate the effectiveness and safety of double-dose osimertinib combined with a pemetrexed intrathecal injection. This is an older man who underwent thoracoscopic pneumonectomy and was diagnosed with stage IIA lung adenocarcinoma with EGFR21 L858R mutation. He experienced thoracic vertebral metastases 33 months postoperatively and received first-line treatment with gefitinib combined with radiotherapy for vertebral metastases. However, the patient developed a grade 3 rash with unacceptable toxicity and his CEA levels were significantly increased 22 months later, leading to a targeted treatment adjustment to 80 mg of osimertinib orally once daily. Four months later, the patient developed LM and osimertinib dosage was increased to 160 mg once daily; however, neurological symptoms did not improve, and cerebrospinal fluid (CSF) tumor cells remained detected. Accordingly, the patient received an intrathecal injection of pemetrexed (dose 30 mg) every 2-3 months, 2-3 times per course (4-6 days each time), and continued to receive a double dose of osimertinib. After three courses of intrathecal chemotherapy, CSF tumor cells were eliminated, and neurological symptoms significantly improved. During the treatment, he experienced a one-degree rash, leukopenia, thrombocytopenia, and fatigue. This patient has been alive and well with disease control for 28 months since the diagnosis of meningeal metastases. Combining double-dose osimertinib and an intrathecal injection of pemetrexed demonstrated therapeutic efficacy and manageable adverse effects in this patient with advanced NSCLC with EGFR-mutant and LM.

BackgroundVitiligo-like depigmentation is a common skin adverse event in patients receiving immunotherapy for malignant melanoma, but has been rarely reported in patients with non-melanoma malignancies. To better understand this immune-related adverse event, we reviewed a series of cases of immunotherapy induced vitiligo-like depigmentation in patients with cancers other than malignant melanoma.Case presentationWe report three cases of vitiligo-like depigmentation after immune checkpoint inhibitor treatment in gastric adenocarcinoma, lung adenocarcinoma, and squamous cell carcinoma. The first case was treated with camrelizumab, the second was treated with QL1706 injection and sintilimab, and the third was treated with tislelizumab. Pembrolizumab, nivolumab, and ipilimumab caused the majority of vitiligo-like depigmentation, and all three of our patients experienced similar vitiligo-like depigmentation after taking other immune checkpoint inhibitors.MethodsThree patients who presented with vitiligo-like depigmentation after treatment with immune checkpoint inhibitors were selected. The clinical features, including radiological and histological examination, and the treatment process were reviewed. Eighteen previously published cases of vitiligo-like depigmentation were also used to analyze the results. The severity of vitiligo-like depigmentation in these cases was graded according to the Common Terminology Criteria for Adverse Events, version 5.0.ResultsVitiligo-like depigmentation occurred in 13 men (61.90%) and 8 women (38.10%), aged from 46 to 79 years, with an average age of 69.9 years. Of the 21 reviewed cases, vitiligo-like depigmentation was described in lung cancer (13/21, 61.90%), clear cell renal cell carcinoma (2/21, 9.52%), acute myeloid leukemia (1/21, 4.76%), cholangiocarcinoma (1/21, 4.76%), urothelial carcinoma (1/21, 4.76%), oral squamous cell carcinoma (1/21, 4.76%), esophageal squamous cell carcinoma (1/21, 4.76%), and gastric adenocarcinoma (1/21, 4.76%). The severity of vitiligo-like depigmentation after immunotherapy was unrelated to sex, age, cancer type, previous autoimmune diseases, and medication.ConclusionsVitiligo-like depigmentation is a non-specific skin adverse event in melanoma immunotherapy, but arises as a direct result of treatment with immune checkpoint inhibitors. Vitiligo-like depigmentation has an irregular location, is not limited to direct sunlight cracks, and has also been reported on hair on the head, eyelashes, and eyebrows. People without any skin or autoimmune diseases can also experience vitiligo-like depigmentation after immunotherapy; the incidence of which is irrespective of sex, age, cancer type, previous autoimmune diseases, and medication.

The Warburg effect, one of the hallmarks of tumors, produces large amounts of lactate and generates an acidic tumor microenvironment via using glucose for glycolysis. As a metabolite, lactate not only serves as a substrate to provide energy for supporting cell growth and development but also acts as an important signal molecule to affect the biochemical functions of intracellular proteins and regulate the biological functions of different kinds of cells. Notably, histone lysine lactylation (Kla) is identified as a novel post-modification and carcinogenic signal, which provides the promising and potential therapeutic targets for tumors. Therefore, the metabolism and functional mechanism of lactate are becoming one of the hot fields in tumor research. Here, we review the production of lactate and its regulation on immunosuppressive cells, as well as the important role of Kla in hepatocellular carcinoma. Lactate and Kla supplement the knowledge gap in oncology and pave the way for exploring the mechanism of oncogenesis and therapeutic targets. Research is still needed in this field.

Background: Cisplatin is the basis of the primary treatment for SCLC chemotherapy. However, the limited objective response rate and definite drug resistance greatly restrict the clinical potential and therapeutic benefits of cisplatin use. Therefore, it is essential to identify biomarkers that can discern the sensitivity of SCLC patients to cisplatin treatment.Methods: We collected two SCLC cohorts treated with cisplatin that included mutation data, prognosis data and expression data. The sensitivity of cisplatin was evaluated by the pRRophetic algorithm. MCPcounter, quanTIseq, and xCell algorithms were used to evaluate immune cell score. GSEA and ssGSEA algorithms were used to calculate immune-related pathway scores. Univariate and multivariate Cox regression models were employed, and survival analysis was used to evaluate the prognostic value of the candidate genes.Results: MMP9-High is related to improved clinical prognoses of patients with SCLC (HR = 0.425, p = 0.0085; HR = 0.365, p = 0.0219). Multivariate results showed that MMP-High could be used as an independent predictor of the prognosis of SCLC after cisplatin treatment (HR = 0.216, p = 0.00153; HR = 0.352; p = 0.0199). In addition, MMP9-High displayed a significantly lower IC50 value of cisplatin and higher immunogenicity than MMP9-Low SCLC. Compared with MMP9-Low SCLC, MMP9-High included significantly increased levels of T-cells, cytoxic lymphocytes, B-cells, NK-cells, and dense cells (DCS). Similarly, the activity of cytokine binding, B-cell, NK-cell mediated immune response chemokine binding, and antigen presentation pathways in MMP9-High was significantly higher than that in MMP9-Low.Conclusion: In this study, we identified that MMP9-High could be potentially considered a novel biomarker used to ascertain the improved prognosis of SCLC patients after cisplatin treatment. Furthermore, we indicated that the tumor immune microenvironment of MMP9-High SCLC is mainly characterized by a large number of infiltrated activated immune cells as well as activated immune-related pathways.

IntroductionGlioblastoma(GBM) is a highly malignant primary brain tumor. Even after undergoing surgery and chemotherapy, patients with this affliction still have little to no chance of survival. Current research on immunotherapy treatment for GBM shows that immune-checkpoint inhibitors (ICIs) may be a promising new treatment method. However, at present, the relationship between the fatty acid metabolic process and the prognosis of GBM patients who are receiving immunotherapy is not clear.MethodsFirst, we downloaded a GBM cohort that had been treated with immunotherapy, which included the mutation and prognosis data, and the TCGA-GBM and Jonsson-GBM queues. CIBERSORT and single sample gene set enrichment analysis(ssGSEA) were used to evaluate immune cell scores. Gene set enrichment analysis (GSEA) was used to evaluate the patient’s accessment score. The pRRophetic algorithm was used to evaluate the drug sensitivity of each patient. Univariable and multivariate cox regression analyses, as well as the Kaplan-Meier (KM) method, were used to evaluate the relationship between the fatty acid metabolic process and the prognosis of GBM patients.ResultsThe univariate and multivariate cox regression models showed that the fatty acid metabolic process mutant-type (MT) can be used as an independent predictor of the efficacy of immunotherapy for GBM patients. In addition, fatty acid metabolic process MT is related with significantly longer overall survival (OS) time than the wild-type(WT) variant. However, the mutation status of the fatty acid metabolic process has nothing to do with the prognosis of GBM patients who are receiving conventional treatment. Our analysis showed that fatty acid metabolic process MT correlated with significantly increased natural killer T (NKT) cells and significantly decreased CD8+T cells. At the same time, GSEA analysis revealed that fatty acid metabolic process MT was associated with significantly increased immune activation pathways and an enriched fraction of cytokine secretion compared with WT.ConclusionsWe found that fatty acid metabolic process MT may be used as an independent predictor of the efficacy of ICI treatment in GBM patients. Use of the fatty acid metabolic process MT will result in higher immunogenicity rates, a significant increase in the proportion of activated immune cells, and improvement of the immune microenvironment.