Programmed cell death protein 1/programmed cell death ligand 1 (PD-1/PD-L1) is a negative modulatory signaling pathway for activation of T cell. It is acknowledged that PD-1/PD-L1 axis plays a crucial role in the progression of tumor by altering status of immune surveillance. As one of the most promising immune therapy strategies, PD-1/PD-L1 inhibitor is a breakthrough for the therapy of some refractory tumors. However, response rate of PD-1/PD-L1 inhibitors in overall patients is unsatisfactory, which limits the application in clinical practice. Therefore, biomarkers which could effectively predict the efficacy of PD-1/PD-L1 inhibitors are crucial for patient selection. Biomarkers reflecting tumor immune microenvironment and tumor cell intrinsic features, such as PD-L1 expression, density of tumor infiltrating lymphocyte (TIL), tumor mutational burden, and mismatch-repair (MMR) deficiency, have been noticed to associate with treatment effect of anti-PD-1/anti-PD-L1 therapy. Furthermore, gut microbiota, circulating biomarkers, and patient previous history have been found as valuable predictors as well. Therefore establishing a comprehensive assessment framework involving multiple biomarkers would be meaningful to interrogate tumor immune landscape and select sensitive patients.

Immune checkpoint inhibitor (ICI) activates host’s anti-tumor immune response by blocking negative regulatory immune signals. A series of clinical trials showed that ICI could effectively induce tumor regression in a subset of advanced cancer patients. In clinical practice, a main concerning for choosing ICI is the low response rate. Even though multiple predictive biomarkers such as PD-L1 expression, mismatch-repair deficiency, and status of tumor infiltrating lymphocytes have been adopted for patient selection, frequent resistance to ICI monotherapy has not been completely resolved. However, some recent studies indicated that ICI resistance could be alleviated by combination therapy with anti-angiogenesis treatment. Actually, anti-angiogenesis therapy not only prunes blood vessel which is essential to cancer growth and metastasis, but also reprograms the tumor immune microenvironment. Preclinical studies demonstrated that the efficacy of combination therapy of ICI and anti-angiogenesis was superior to monotherapy. In mice model, combination therapy could effectively increase the ratio of anti-tumor/pro-tumor immune cell and decrease the expression of multiple immune checkpoints more than PD-1. Based on exciting results from preclinical studies, many clinical trials were deployed to investigate the synergistic effect of the combination therapy and acquired promising outcome. This review summarized the latest understanding of ICI combined anti-angiogenesis therapy and highlighted the advances of relevant clinical trials.

During tumor progression, a subset of cancer cells escape from immune surveillance and eventually develop into measurable tumor mass. Cancer immunotherapy eradicates tumor cells by enhancing multiple steps in cancer-immunity cycle including antigen presentation, T cell priming, activation, and immune killing activity. Immunotherapy has been verified as an effective strategy in multiple cancers, but some problems still exist in actual clinical practice such as frequent primary and adaptive resistance. Combination with other adjuvant therapies gives us a new perspective to overcome the emerging obstacles in immunotherapy application. Recently, a series of studies demonstrated that the vital component of host innate immunity — cGAS-STING pathway might play an important role in anti-cancer immunity. It is generally acknowledged that the downstream signals of cGAS-STING especially type I interferon (IFN) bridge innate immunity and adaptive immunity. Given the functions of type I IFN in promoting the maturation and migration of dendritic cells, enhancing cytotoxic T lymphocyte- or natural killer cell-mediated cytotoxicity effect, and protecting effector cells from apoptosis, we believe cGAS-STING agonist might be used as sensitizer for multiple immunotherapies such as cancer vaccine, immune checkpoint blockade, and chimeric antigen receptor T cell therapy. In this review, we highlight the latest understanding of cGAS-STING pathway and the advances of the combination therapy of STING agonist and immunotherapy.

Triple-negative breast cancer (TNBC), a highly aggressive subtype of breast cancer, negatively expresses estrogen receptor, progesterone receptor, and the human epidermal growth factor receptor 2 (HER2). Although chemotherapy is the main form of treatment for patients with TNBC, the effectiveness of chemotherapy for TNBC is still limited. The search for more effective therapies is urgent. Multiple targeted therapeutic strategies have emerged according to the specific molecules and signaling pathways expressed in TNBC. These include PI3K/AKT/mTOR inhibitors, epidermal growth factor receptor inhibitors, Notch inhibitors, poly ADP-ribose polymerase inhibitors, and antibody–drug conjugates. Moreover, immune checkpoint inhibitors, for example, pembrolizumab, atezolizumab, and durvalumab, are widely explored in the clinic. We summarize recent advances in targeted therapy and immunotherapy in TNBC, with the aim of serving as a reference for the development of individualized treatment of patients with TNBC in the future.

During the past decade, the three-dimensional organoid technology has sprung up and become more and more popular among researchers. Organoids are the miniatures of in vivo tissues and organs, and faithfully recapitulate the architectures and distinctive functions of a specific organ. These amazing three-dimensional constructs represent a promising, near-physiological model for human cancers, and tremendously support diverse potential applications in cancer research. Up to now, highly efficient establishment of organoids can be achieved from both normal and malignant tissues of patients. Using this bioengineered platform, the links of infection-cancer progression and mutation-carcinogenesis are feasible to be modeled. Another potential application is that organoid technology facilitates drug testing and guides personalized therapy. Although organoids still fail to model immune system accurately, co-cultures of organoids and lymphocytes have been reported in several studies, bringing hope for further application of this technology in immunotherapy. In addition, the potential value in regeneration medicine might be another paramount branch of organoid technology, which might refine current transplantation therapy through the replacement of irreversibly progressively diseased organs with isogenic healthy organoids. In conclusion, organoids represent an excellent preclinical model for human tumors, promoting the translation from basic cancer research to clinical practice. In this review, we outline organoid technology and summarize its applications in cancer research.

Angiogenesis has always been the topic of major scientific interest in the field of malignant tumors. Nowadays, targeting angiogenesis has achieved success in various carcinomas by several mechanisms, including the use of anti-angiogenic small molecule receptor tyrosine kinase inhibitors (TKIs). The development of TKIs targeting pro-angiogenic receptors, mainly vascular endothelial growth factor receptor (VEGFR) family, have significantly improved the outcome of certain types of cancers, like renal cell carcinoma, hepatocellular carcinoma, and colorectal carcinoma. However, the general response rate is not very satisfactory. The particular toxicity profile and resistance to anti-angiogenic targeted agents are unavoidable, and no specific marker is available to screen responsive patients to TKIs for precision therapy. To date, about 11 anti-angiogenic TKIs with different binding capacities to angiogenic receptor tyrosine kinase have been approved for the treatment of patients with advanced cancers. This review presents all approved anti-angiogenic small molecule receptor TKIs so far with an emphasis on their indications and clinical efficacy. We also discuss the combination between TKIs and immune checkpoint blockade inhibitors based on the most recent exciting outcome in immunotherapy.