PD-1/PD-L1 blockade therapy is a promising cancer treatment strategy, which has revolutionized the treatment landscape of malignancies. Over the last decade, PD-1/PD-L1 blockade therapy has been trialed in a broad range of malignancies and achieved clinical success. Despite the potentially cure-like survival benefit, only a minority of patients are estimated to experience a positive response to PD-1/PD-L1 blockade therapy, and the primary or acquired resistance might eventually lead to cancer progression in patients with clinical responses. Accordingly, the resistance to PD-1/PD-L1 blockade remains a significant challenge hindering its further application. To overcome the limitation in therapy resistance, substantial effort has been made to improve or develop novel anti-PD-1/PD-L1 based immunotherapy strategies with better clinical response and reduced immune-mediated toxicity. In this review, we provide an overview on the resistance to PD-1/PD-L1 blockade and briefly introduce the mechanisms underlying therapy resistance. Moreover, we summarize potential predictive factors for the resistance to PD-1/PD-L1 blockade. Furthermore, we give an insight into the possible solutions to improve efficacy and clinical response. In the following research, combined efforts of basic researchers and clinicians are required to address the limitation of therapy resistance.

The introduction of immunotherapies has been a major development in the treatment of many advanced cancers, including hepatocellular carcinoma (HCC). We are entering a new era of systemic therapy for advanced HCC associated with an explosion of clinical trial activity. Data from phase I/II studies of checkpoint inhibitors in advanced HCC have been promising, with durable objective response rates of approximately 20% seen (in both first- and second-line settings) and acceptable safety profiles (including immune-mediated hepatitis). Phase III studies evaluating anti-programmed cell death protein 1 (anti-PD-1) and anti-programmed cell death ligand 1 (anti-PD-L1) antibodies compared with sorafenib are already underway. The potential synergistic effects of anti-PD-1/anti-PD-L1 when used in combination with agents against other checkpoint molecules, systemic therapies, as well as conventional surgical and locoregional therapies are also being explored in upcoming clinical trials. Aside from this, other strategies to harness the immune system, including chimeric antigen receptor-engineered T cells, natural killer cell therapies, and peptide vaccines directed against HCC antigens have entered phase I/II studies. Current limitations of immunotherapies and areas of future research include the accurate assessment and prediction of tumor response, overcoming the immunosuppressive effects of a hypoxic microenvironment, and the management of immune-related hepatitis in patients who already have limited liver reserve.

Breast cancer is the most common malignant tumor in women in the majority of countries, such as China, Britain and Australia, and its morbidity and mortality rates remain very high. Long non‑coding RNAs (lncRNAs) are non‑coding RNAs (ncRNAs) >200 nucleotides in length that lack open reading frames. LncRNA H19 is a transcription product of the H19 gene, and the aberrant expression of H19 can be demonstrated in various types of tumor cell. The purpose of the present review was to elaborate the role of H19 in breast cancer. H19 can regulate gene expression in breast cancer at multiple levels, including epigenetic, transcriptional and posttranscriptional. The abnormal expression of H19 is closely associated with the tumorigenesis and progression of breast cancer via different underlying molecular mechanisms, such as encoding microRNA‑675, competing endogenous RNA regulation and interacting with MYC. A large number of clinical studies have suggested that H19 can serve as a potential biomarker for the diagnosis of breast cancer. High expression levels of H19 increases the drug resistance of breast cancer cells and is associated with poor prognosis within patients with breast cancer. Therefore, serum H19 levels may have momentous significance in the clinical setting.