The development of cancer immunotherapy, particularly immune checkpoint blockade therapy, has made major breakthroughs in the therapy of cancers. However, less than one-third of the cancer patients obtain significant and long-lasting therapeutic effects by cancer immunotherapy. Over the past few decades, cancer-related inflammations have been gradually more familiar to us. It’s known that chronic inflammation in tumor microenvironment (TME) plays a predominant role in tumor immunosuppression. Tumor-associated extracellular matrix (ECM), as a core member of TME, has been a research hotspot recently. A growing number of studies indicate that tumor-associated ECM is one of the major obstacles to realizing more successful cases of cancer immunotherapy. In this review, we discussed the potential application of tumor-associated ECM in the cancer immunity and its aide potentialities to anti-tumor immunotherapy.

Purpose: ACT001 is a novel sesquiterpene lactone derivative with anticancer effects, including the reversal of tamoxifen resistance in estrogen receptor-positive breast cancer cells. However, few studies have investigated the anticancer effects of ACT001 in triple-negative breast cancer (TNBC), a highly aggressive cancer with a poor prognosis. This study aimed to investigate the effects of ACT001 on TNBC and the potential mechanism underlying these effects. Materials and Methods: The anticancer effects of ACT001 on the murine TNBC cell line 4T1 were evaluated by Cell Counting Kit-8 assay, animal experiments, TUNEL staining, flow cytometry, immunofluorescence, enzyme-linked immunosorbent assay, and Western blotting analysis. Results: ACT001 induced apoptosis in 4T1 cells by upregulating B cell lymphoma 2-associated X protein expression. Moreover, ACT001 markedly decreased levels of secretory granulocyte-macrophage colony stimulating factor (GM-CSF) in 4T1 tumors, decreased the number of myeloid-derived suppressor cells (MDSCs), and reduced angiogenesis. Furthermore, GM-CSF promoted angiogenesis and the proliferation of MDSCs in a dose-dependent manner. Finally, ACT001 suppressed phospho-NF-κB and IκB-α levels in 4T1 cells, thereby further decreasing GM-CSF levels. Conclusion: Our results suggest that ACT001 exerts its anticancer effects by inducing apoptosis in murine TNBC cell line 4T1 and regulates the tumor microenvironment by attenuating angiogenesis and accumulation of MDSCs in 4T1 tumors. The underlying mechanism may involve the suppression of NF-κB activity.

Immune checkpoint inhibitors (ICIs) are monoclonal antibody antagonists, which can block cytotoxic T lymphocyte antigen-4 (CTLA-4), programmed death-1/ligand-1 (PD-1/PD-L1) pathways, and other molecules exploited by tumor cells to evade T cell-mediated immune response. ICIs have transformed the treatment landscape for various cancers due to their amazing efficacy. Many anti-tumor therapies, including targeted therapy, radiotherapy, and chemotherapy, combine ICIs to make the treatment more effective. However, the off-target immune activation caused by ICIs may lead to a broad spectrum of immune-related adverse events (irAEs) affecting multiple organ systems. Among irAEs, cardiotoxicity induced by ICIs, uncommon but fatal, has greatly offset survival benefits from ICIs, which is heartbreaking for both patients and clinicians. Consequently, such cardiotoxicity requires special vigilance, and it has become a common challenge both for patients and clinicians. This article reviewed the clinical manifestations and influence of cardiotoxicity from the view of patients and clinicians, elaborated on the underlying mechanisms in conjunction with animal studies, and then attempted to propose management strategies from a cardio-immuno-oncology multidisciplinary perspective.

Rationale: Non-small cell cancer with isolated unilateral renal metastasis is rare, and the role of radical nephrectomy has not been determined. In the present study, a case of a patient with solitary kidney metastasis from squamous cell lung cancer who underwent radical nephrectomy is reported. Patient concerns: A 74-year-old patient diagnosed with pulmonary squamous cell lung cancer who had undergone radical pulmonary lobectomy and mediastinal lymph node dissection revealed a solitary mass in the right kidney during the follow-up. Diagnoses: Unilateral isolated kidney metastasis originated from squamous cell lung cancer. Interventions: The patient underwent radical right nephrectomy and squamous cell cancer metastasis was confirmed by the postoperative pathology results. Outcome: Lung cancer relapse was diagnosed and the patient died of cancer progression 10 months after the right nephrectomy. Lessons: Solitary renal metastasis is rare and squamous cell lung cancer might be the primary disease. Abdominal computed tomography (CT) is important in detecting solitary kidney metastasis during the follow up of patients with squamous cell lung cancer. Due to the rareness of isolated renal metastasis, the role of radical nephrectomy needs to be further investigated.

The development of various therapeutic interventions, particularly immune checkpoint inhibitor therapy, have effectively induced tumor remission for patients with advanced lung cancer. However, few cancer patients can obtain significant and long-lasting therapeutic effects for the limitation of immunological nonresponse and resistance. For this case, it’s urgent to identify new biomarkers and develop therapeutic targets for future immunotherapy. Over the past decades, tumor microenvironment (TME)-related long non-coding RNAs (lncRNAs) have gradually become well known to us. A large number of existing studies have indicated that TME-related lncRNAs are one of the major factors to realize precise diagnosis and treatment of lung cancer. Herein, this paper discusses the roles of lncRNAs in TME, and the potential application of lncRNAs as biomarkers or therapeutic targets for immunotherapy in lung cancer.

Background: Tumor immune microenvironment plays a vital role in tumorigenesis and progression of gastric cancer (GC), but potent immune biomarkers for predicting the prognosis have not been identified yet.Methods: At first, RNA-sequencing and clinical data from The Cancer Genome Atlas (TCGA) were mined to identify an immune-risk signature using least absolute shrinkage and selection operator (LASSO) regression and multivariate stepwise Cox regression analyses. Furthermore, the risk score of each sample was calculated, and GC patients were divided into high-risk group and low-risk group based on their risk scores. Subsequently, the performance of this signature, including the correlation with overall survival (OS), clinical features, immune cell infiltration, and immune response, has been tested in GC data from TCGA database and Gene Expression Omnibus (GSE84437), respectively.Results: An immune signature composed of four genes (MAGED1, ACKR3, FZD2, and CTLA4) was constructed. The single sample gene set enrichment analysis (ssGSEA) indicated that activated CD4⁺/CD8⁺ T cell, activated dendritic cell, and effector memory CD8⁺ T cell prominently increased in the low-risk group, showing relatively high immune scores and low stromal scores. Further GSEA analysis indicated that TGF-β, Ras, and Rap1 pathways were activated in the high-risk group, while Th17/Th1/Th2 differentiation, T cell receptor and PD-1/PD-L1 checkpoint pathways were activated in the low-risk group. Low-risk patients presented higher tumor mutation burden (TMB) and expression of HLA-related genes. The immune-associated signature showed an excellent predictive ability for 2-, 3-, and 5-year OS in GC.Conclusion: The immune-related prognosis model contributes to predicting the prognosis of GC patients and providing valuable information about their response to immunotherapy using integrated bioinformatics methods.