The recent impressive clinical responses to antibody-based immunotherapy have prompted the identification of clinically relevant tumor antigens that can serve as targets in solid tumors. Among them, B7-H3, a member of the B7 ligand family, represents an attractive target for antibody-based immunotherapy, it is overexpressed on differentiated malignant cells and cancer-initiating cells, with limited heterogeneity, and high frequency (60% of 25,000 tumor samples) in many different cancer types, but has a limited expression at low level in normal tissues. In nonmalignant tissues, B7-H3 has a predominantly inhibitory role in adaptive immunity, suppressing T-cell activation and proliferation. In malignant tissues, B7-H3 inhibits tumor antigen–specific immune responses, leading to a protumorigenic effect. B7-H3 also has nonimmunologic protumorigenic functions, such as promoting migration and invasion, angiogenesis, chemoresistance, and endothelial-to-mesenchymal transition, as well as affecting tumor cell metabolism. As a result, B7-H3 expression in tumors is associated with poor prognosis. Although experimental B7-H3 silencing reduces cancer cell malignant potential, there has been limited emphasis on the development of B7-H3–blocking antibodies, most likely because the B7-H3 receptor remains unknown. Instead, many antibody-based strategies utilizing distinct effector mechanisms to target B7-H3–expressing cancer cells have been developed. These strategies have demonstrated potent antitumor activity and acceptable safety profiles in preclinical models. Ongoing clinical trials are assessing their safety and efficacy in patients. Identification of the B7-H3 receptor will improve our understanding of its role in tumor immunity, and will suggest rational strategies to develop blocking antibodies, which may enhance the therapeutic efficacy of tumor immunity.

Background Neoadjuvant FOLFIRINOX and chemoradiation have been utilized to downstage borderline and locally advanced pancreatic ductal adenocarcinoma (PDAC). Whether neoadjuvant therapy-induced tumor immune response contributes to the improved survival is unknown. Therefore, we evaluated whether neoadjuvant therapy induces an immune response towards PDAC. Methods Clinicopathologic variables were collected for surgically resected PDACs at the Massachusetts General Hospital (1998-2016). Neoadjuvant regimens included FOLFIRINOX with/without chemoradiation, proton chemoradiation (25Gy), photon chemoradiation (50.4Gy) or no neoadjuvant therapy. HLA class I and II expression, and immune cell infiltration (CD4+, FoxP3+, CD8+, Granzyme B+ cells and M2 macrophages) were analyzed immunohistochemically and correlated with clinicopathologic variables. The antitumor immune response was compared among neoadjuvant therapy regimens. All statistical tests were two-sided. Results Two hundred forty-eight PDAC patients were included. Median age was 64y; 50.0% were female. HLA-A defects were less frequent in the FOLFIRINOX cohort (p=.006). HLA class II expression was lowest in photon and highest in proton patients (p=.02). The FOLFIRINOX cohort exhibited the densest CD8+ cell infiltration (p<.001). FOLFIRINOX and proton patients had the highest CD4+ and lowest T regulatory (FoxP3+) cell density, respectively. M2 macrophage density was statistically significantly higher in the treatment-naïve group (p<.001), in which dense M2 macrophage infiltration was an independent predictor of poor OS. Conclusions Neoadjuvant FOLFIRINOX with/without chemoradiation may induce immunologically relevant changes in the tumor microenvironment. It may reduce HLA-A defects, increase CD8+ cell density and decrease T regulatory cell and M2 macrophage density. Therefore, neoadjuvant FOLFIRINOX therapy may benefit from combinations with checkpoint inhibitors, which can enhance patients’ antitumor immune response.

Objective Whether cervical disc arthroplasty (CDA) is superior to anterior cervical discectomy and fusion (ACDF) remains controversial, especially in relation to long‐term results. The present study aimed to evaluate the long‐term safety and efficiency of CDA and ACDF for cervical disc disease. Methods We performed this study according to the Cochrane methodology. An extensive search was undertaken in PubMed, Embase, and Cochrane databases up to 1 June 2019 using the following key words: “anterior cervical fusion,” “arthroplasty,” “replacement” and “artificial disc”. RevMan 5.3 (Cochrane, London, UK) was used to analyze data. Safety and efficiency outcome measures included the success rate, functional outcome measures, adverse events (AE), adjacent segment degeneration (ASD), secondary surgery, and patients’ satisfaction and recommendation rates. The OR and MD with 95% confidence interval (CI) were used to evaluate discontinuous and continuous variables, respectively. The statistically significant level was set at P < 0.05. Results A total of 11 randomized controlled trials with 3505 patients (CDA/ACDF: 1913/1592) were included in this meta‐analysis. Compared with ACDF, CDA achieved significantly higher overall success (2.10, 95% CI [1.70, 2.59]), neck disability index (NDI) success (1.73, 95% CI [1.37, 2.18]), neurological success (1.65, 95% CI [1.24, 2.20]), patients’ satisfaction (2.14, 95% CI [1.50, 3.05]), and patients’ recommendation rates (3.23, 95% CI [1.79, 5.80]). Functional outcome measures such as visual analog score neck pain (−5.50, 95% CI [−8.49, −2.52]) and arm pain (−3.78, 95% CI [−7.04, −0.53]), the Short Form‐36 physical component score (SF‐36 PCS) (1.93, 95% CI [0.53, 3.32]), and the Short Form‐36 mental component score (SF‐36 MCS) (2.62, 95% CI [0.95, 4.29]), revealed superiority in the CDA group. CDA also achieved a significantly lower rate of symptomatic ASD (0.46, 95% CI [0.34, 0.63]), total secondary surgery (0.50, 95% CI [0.29, 0.87]), secondary surgery at the index level (0.46, 95% CI [0.29, 0.74]), and secondary surgery at the adjacent level (0.37, 95% CI [0.28, 0.49]). However, no significant difference was found in radiological success (1.35, 95% CI [0.88, 2.08]), NDI score (−2.88, 95% CI [−5.93, 0.17]), total reported AE (1.14, 95% CI [0.92, 1.42]), serious AE (0.89, 95% CI [0.71, 1.11]), device/surgery‐related AE (0.90, 95% CI [0.68, 1.18]), radiological superior ASD (0.63, 95% CI [0.28, 1.43]), inferior ASD (0.45, 95% CI [0.19, 1.11]), and work status (1.33, 95% CI [0.78, 2.25]). Furthermore, subgroup analysis showed different results between US and non‐US groups. Conclusion Our study provided further evidence that compared to ACDF, CDA had a higher long‐term clinical success rate and better functional outcome measurements, and resulted in less symptomatic ASD and fewer secondary surgeries. However, worldwide multicenter RCT with long‐term follow up are still needed for further evaluation in the future.