Background: The composition of the gut microbiota is associated with the response to immunotherapy for different cancers. However, the majority of previous studies have focused on a single cancer and a single immune checkpoint inhibitor. Here, we investigated the relationship between the gut microbiota and the clinical response to anti-programmed cell death protein 1 (PD-1) immunotherapy in patients with advanced cancers. Method: In this comprehensive study, 16S rRNA sequencing was performed on the gut microbiota of pre-immunotherapy and post-immunotherapy, of 72 advanced cancer patients in China. Results: At the phylum level, Firmicutes, Bacteroidetes, Proteobacteria, and Actinobacteria were the main components of the microbiota in the 72 advanced cancer patients. At the genus level, Bacteroides and Prevotella were the dominant microbiota among these 72 patients. The PD_whole_tree, Chao1, Observed_species and Shannon indices of R.0 and R.T were higher than those of NR.0 and NR.T. The results of LEfSe showed that Archaea, Lentisphaerae, Victivallaceae, Victivallales, Lentisphaeria, Methanobacteriaceae, Methanobacteria, Euryarchaeota, Methanobrevibacter, and Methanobacteriales were significantly enriched in the response group before immunotherapy (R.0), and the Clostridiaceae was significantly enriched in the non-response group before immunotherapy (NR.0) (p < 0.05). Lachnospiraceae and Thermus were significantly enriched in the response group after immunotherapy (R.T), and Leuconostoc was significantly enriched in R.0 (p < 0.05). ROC analysis showed that the microbiota of R.T (AUC = 0.70) had obvious diagnostic value in differentiating Chinese cancer patients based on their response to immunotherapy. Conclusions: We demonstrated that the gut microbiota was associated with the clinical response to anti-PD-1 immunotherapy in cancer patients. Taxonomic signatures enriched in responders were effective biomarkers to predict the clinical response. Our findings provide a new strategy to improve the efficiency of responses to immunotherapy among cancer patients.

Rationale: The guidelines recommended gefitinib as a first-line targeted treatment for stage IV non-small-cell lung cancer (NSCLC) patients with EGFR mutations. However, resistance to gefitinib ensues invariably and there is little evidence as for the effectiveness of subsequent salvage treatment for patients without T790m mutation. The case is to evaluate the efficacy of erlotinib, another EGFR-TKI, after failed first-line use of gefitinib. Patient concerns: We described a 55-year-old man with good performance status (PS). Diagnoses: He was histopathologically diagnosed stage IV lung adenocarcinoma with EGFR mutations in November 2018. Interventions: He was administrated with gefitinib daily (250 mg) for activating epidermal growth factor receptor (EGFR) mutations (exon 19 deletions,19del), and combined with platinum-based dual-drug chemotherapy. During the target treatments, the optimal efficacy evaluation was partial remission (PR) with a 12-month progression-free survival (PFS) time. Later, the intracranial progression of the patient rendered the treatment change to erlotinib. Outcomes: It is surprising that the tumor lesion in brain as well as lung relieved obviously. His progression-free survival (PFS)was nearly 11 months, and the overall survival (OS)was>36 months up to now. The adverse events were tolerable. Lessions: This case manifests that re-biopsy of advanced or recurrent NSCLC is beneficial to make a better therapeutic regimen, and erlotinib can be used as a salvage treatment after gefitinib failure.

Rationale: Intimal sarcoma of inferior vena cava (IVC) is a rare soft tissue sarcoma with no typical symptoms and specific imaging features in the early stage, and there is a lack of standardized treatment and methods. Patient concerns: A 54-year-old female patient presented to Fenghua District People’s Hospital with a post-active cough and hemoptysis and was subsequently referred to our hospital. Diagnoses: The patient was pathologically diagnosed as intimal sarcoma of IVC complicating multiple intrapulmonary metastases. Chest CT revealed left lung malignant tumor with multiple intrapulmonary metastases; while enhanced upper abdominal CT showed cancer embolus of IVC with extension to right atrium and bilateral renal veins. Besides, hematoxylin and eosin staining suggested intimal sarcoma of veins. Immunohistochemical staining showed positivity for PD-L1, Ki-67, CD31, Desmin and ERG. Interventions: The patient initially received GT chemotherapy (gemcitabine injection + docetaxel). Then, immunotherapy (tislelizumab) was added based on the results of genetic testing (TP53 gene mutation). Outcomes: The disease was stabilized after receiving the treatment. Lessons: Given the lack of characteristic clinical manifestations in patients with intimal sarcoma of IVC, imaging examination combined with immunohistochemical index were helpful for diagnosis of intimal sarcoma of IVC. Furthermore, the combination of tislelizumab and GT chemotherapy was feasible in such patients with positive PD-L1 expression and TP53 mutation.

Melanoma is a malignant tumor that originates in melanocytes of the skin or mucous membrane, which has a high mortality rate and worse prognosis. Therefore, perspective prognosis evaluation seems more important for patients treatment. Gene expression profiles of melanoma were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, respectively. 130 consistent differentially expressed genes (DEGs) were identified between melanoma and nevus tissues from two GEO cohorts. Prognostic genes were identified by univariate analysis, and 20 of them were regarded to be associated with the recurrence-free survival (RFS) of melanoma patients. Then, the LASSO Cox regression analysis chose seven of them to establish a seven-DEG-based RFS predicting signature. We demonstrated that this model was more powerful to predict RFS risk than other individual clinical features and was able to independently predict the RFS outcomes in different subsets of patients. We attempted to search for the underlying mechanisms by analyzing the coexpression genes of the seven candidates, and the pathway enrichment analyses indicated that immune response-related pathways might play a critical role in melanoma progression. Finally, we establish a robust seven-DEG-based RFS predicting signature, which will facilitate the personalized treatment of melanoma patients.

Metal ions are key regulators of the neuro–immune–tumor axis. Recent studies provide concrete evidence that neuronal Ca ²⁺ pulses drive tumor–neuron integration and shape immune signaling. Synaptic Zn ²⁺ and ZIP transporters modulate synaptic transmission and tumor growth. Tumor iron accumulation fuels proliferation while creating a clear ferroptosis vulnerability. Copper promotes angiogenesis, lysyl oxidase (LOX)‐mediated extracellular matrix (ECM) remodeling and metastasis, and implicates cuproptosis as a therapeutic target. Mn potentiates cyclic GMP‐AMP synthase (cGAS)–STING signaling and serves as both an immune adjuvant and manganese‐enhanced magnetic resonance imaging (MEMRI) contrast. Besides, Mg and K ⁺ regulate kinase/T‐cell receptor (TCR) function and tumor–neuron excitability, respectively. Despite these advances, major gaps persist, notably limited spatial and temporal mapping of labile metal pools, a paucity of cell‐type‐specific causal perturbations, and underdeveloped tumor‐targeted metal‐modulating therapies with proven safety. We therefore propose a focused research agenda: integrate spatial metallomics with single‐cell multiomics, deploy metal‐sensitive longitudinal imaging, apply conditional genetic and chemogenetic perturbations and organotypic models to dissect neuro–immune cross‐talk, and implement preclinical pipelines emphasizing tumor‐selective delivery and comprehensive safety testing.