PD-1/PD-L1 blockade therapies have displayed extraordinary clinical efficacy for melanoma, renal, bladder and lung cancer; however, only a minority of colorectal cancer (CRC) patients benefit from these treatments. The efficacy of PD-1/PD-L1 blockade in CRC is limited by the complexities of tumor microenvironment. PD-1/PD-L1 blockade immunotherapy is based on T cell-centered view of tumor immunity. However, the onset and maintenance of T cell responses and the development of long-lasting memory T cells depend on innate immune responses. Acknowledging the pivotal role of innate immunity in anti-tumor immune response, this review encapsulates the employment of combinational therapies those involve PD-1/PD-L1 blockade alongside the activation of innate immunity and explores the underlying cellular mechanisms, aiming to harnessing innate immune responses to induce long-lasting tumor control for CRC patients who received PD-1/PD-L1 blockade therapy.

Purpose: To evaluate the dynamics of early serum tumour markers (STMs) and the neutrophil-to-lymphocyte ratio (NLR) to predict clinical efficacy and prognosis of advanced non-small-cell lung cancer (NSCLC) patients who received programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) inhibitors. Patients and Methods: We retrospectively reviewed patients with advanced NSCLC treated with PD-1/PD-L1 inhibitors between September 2017 and August 2020. NLR and STMs were routinely measured between immunotherapy initiation and the first radiological evaluation. A combination score based on the leading STM and NLR and their dynamic changes was established. The effects of leading STM change, NLR change, and the combination score on the objective response rate (ORR), durable clinical benefit (DCB), progression-free survival (PFS), and overall survival (OS) were analysed. The accuracy of the combination score was evaluated by receiver operating characteristic (ROC) curve and the area under the curve (AUC). Results: Overall, 124 patients were included in this retrospective cohort study. The ORR was 22.8%, DCB was 54.5%, and the median OS and PFS were 21.6 and 14.9 months, respectively. Patients with low combination scores had a significantly improved ORR and DCB compared with those with intermediate or high scores (P = 0.002 for ORR, P < 0.0001 for DCB). In a multivariate model, the combination score was an independent indicator of PFS (P < 0.0001) and OS (P < 0.0001). The AUC demonstrated that the combination score (AUC = 0.706) has greater predictive power than either the posttreatment NLR (AUC = 0.668) or the leading STM change (AUC = 0.648) alone. Conclusion: An easy, cost-effective, and novel combination score based on the dynamics of an early STM and the NLR can accurately predict the clinical efficacy of PD-1/PD-L1 inhibitors and prognosis in advanced NSCLC patients.

Primary squamous cell carcinoma (SCC) of the liver is an uncommon cancer type. Only dozens of such cases have been reported in the literature. We reviewed three cases with primary SCC of the liver in a single center from January 2013 to October 2019. One case was positive for hepatitis B infection and simultaneously diagnosed with sigmoid adenocarcinoma and liver cyst. The second patient presented with hepatolithiasis. The remaining one had no history of prior liver insult, hepatic infection or any pre-existing hepatic cysts. Two cases had a long survival of more than one year through chemotherapy, or radical surgery plus transarterial chemoembolization. We also found 25 patients with primary hepatic SCC in the Surveillance, Epidemiology and End Results (SEER) database from 1997 to 2016. The median age was 67 years (range 33– 87 years). The median overall survival and disease-specific survival were 7.7 months (range 0.0– 76.0 months) and 2.0 months (range 0.0– 20.0 months), respectively. Furthermore, patients receiving surgery had a longer median OS (20.0 versus 6.0 months, P = 0.016) and DSS (48.0 versus 8.0 months, P = 0.03) than those receiving palliative treatment. Only 20% of all cases survived for more than a year. Although primary SCC of the liver has an unfavorable prognosis, radical surgery and systematic treatment might be helpful for clinical management.

Microbiota has been closely related to human beings, whose role in tumor development has also been widely investigated. However, previous studies have mainly focused on the gut, oral, and/or skin microbiota. In recent years, the study of intratumoral microbiota has become a hot topic in tumor-concerning studies. Intratumoral microbiota plays an important role in the occurrence, development, and response to treatment of malignant tumors. In fact, increasing evidence has suggested that intratumoral microbiota is associated with malignant tumors in various ways, such as promoting the tumor development and affecting the efficacy of chemotherapy and immunotherapy. In this review, the impact of intratumoral microbiota on the immune microenvironment of malignant tumors has been analyzed, as well as its role in tumor immunotherapy, with the hope that it may contribute to the development of diagnostic tools and treatments for related tumors in the future.

System induced by the death of immunogenic tumor cells. Here, we have presented the case of a 65-year-old woman with primary endometrial cancer who developed bilateral pulmonary metastases. After local MWA of one lesion in her right lung, progressive regression of the other lesions in the right and left lungs was recorded. This case supports the hypothesis that the abscopal effect is attributable to the activation of the systemic immune response....

Endostatin has previously been demonstrated to efficiently inhibit the angiogenesis and growth of endothelial cells. However, the role of endostatin in the tumor microenvironment remains to be elucidated. To investigate the antitumor effect of endostatin in lung cancer, the present study was designed to explore the alterations of microvessel density in Lewis lung cancer models and the expression of vascular endothelial growth factor (VEGF), interleukin (IL)‑6, IL‑17, interferon (IFN)‑γ and hypoxia inducible factor (HIF)‑1α, following endostatin therapy. It was demonstrated that the growth and angiogenesis of tumors were markedly suppressed by treatment with endostatin, compared with control group. The microvessel density in mice treated with endostatin was significantly inhibited in a dose‑dependent manner. The expression levels of VEGF, IL‑6 and IL‑17 in tumors were decreased, however IFN‑γ and HIF‑1α expression levels were increased, following treatment with endostatin. In addition, the proportion of myeloid derived suppressor cells and tumor associated macrophages (TAMs; M2 type) were significantly decreased, whereas those of mature dendritic cells and TAMs (M1 type) were increased, and cluster of differentiation (CD)8+ T cells were recruited to infiltrate the tumors following treatment with endostatin. In addition, the expression levels of IL‑6, IL‑10, tumor growth factor‑β and IL‑17 in tumor tissue were potently decreased with endostatin therapy. These results indicated that endostatin efficiently inhibited tumor angiogenesis and reversed the immunosuppressive microenvironment associated with the presence of tumors.