Generic and Specific Social Learning Mechanisms in Foreign Entry Location Choice

We combine economic and institutional theories of clustering in foreign entry location choice in an overarching social learning conceptualization. Prospective entrants learn about the attractiveness of alternative locations by observing the entry choices of previous investors ('models'). We distinguish two types of learning that differ in observational focus width but can and do operate simultaneously. With assessment learning, firms judge the economic feasibility and agglomeration benefits of entering a location by observing and following a broad set of models. With bandwagon learning, firm-level uncertainty narrows attention to, and prompts the following of, specific models, with recentness of model behavior an important moderator. We find broad support for our conceptualization in an analysis of the entries of 692 Japanese electronics firms into Chinese provinces during 1979-2001

Combination of PD-1/PD-L1 checkpoint inhibition and dendritic cell therapy in mice models and in patients with mesothelioma

Immunotherapy with anti-PD1/PD-L1 is effective in only a subgroup of patients with malignant pleural mesothelioma (MPM). We investigated the efficacy of a combination of anti-PD1/PD-L1 and dendritic cell (DC) therapy to optimally induce effective anti-tumor immunity in MPM in both humans and mice. Data of nine MPM patients treated with DC therapy and sequential anti-PD1 treatment were collected and analyzed for progression-free survival (PFS) and overall survival (OS). Survival and T-cell responses were monitored in AC29 mesothelioma-bearing mice treated concurrently with the combination therapy; additionally, the role of the tumor-draining lymph node (TDLN) was investigated. The combination therapy resulted in a median OS and PFS of 17.7 and 8.0 months, respectively. Grade 3 to 4 treatment-related adverse events had not been reported. Survival of the mesothelioma-bearing mice treated with the combination therapy was longer than that of untreated mice, and coincided with improved T-cell activation in peripheral blood and less T-cell exhaustion in end stage tumors. Comparable results were obtained when solely the TDLN was targeted. We concluded that this combination therapy is safe and shows promising OS and PFS. The murine data support that PD-L1 treatment may reinvigorate the T-cell responses induced by DC therapy, which may primarily be the result of TDLN targeting

High-intensity statins are associated with improved clinical activity of PD-1 inhibitors in malignant pleural mesothelioma and advanced non-small cell lung cancer patients

Background: In preclinical models, statins showed vaccine adjuvant activities and synergized with PD-1 inhibitors. We analyzed the impact of statin treatment on clinical outcome in thoracic cancer patients treated with PD-1 inhibitors. Methods: A total of 82 malignant pleural mesothelioma (MPM) and 179 advanced non-small cell lung cancer (aNSCLC) patients treated with PD-1 inhibitors as second or further line treatment were examined. Seventy-seven MPM patients treated with standard chemotherapy were analyzed as control cohort. Objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) were calculated. Results: Among 253 patients with available data, statin use was associated with increased ORR (32% versus 18%, P =.02), PFS (median 6.7 versus 2.9 months, hazard ratio [HR] 0.57, 95% CI 0.39–0.83, P <.01), and OS (median 13.1 versus 8.7 months, HR 0.67, 95% CI 0.45–1.00, P =.05). In the control MPM cohort treated with chemotherapy (n = 77), no association was found. MPM patients who used statins showed improved ORR (22% versus 6%, P =.05), PFS (median 6.7 versus 2.4 months, P <.01), and OS (median not reached versus 6.0 months, P =.01). In aNSCLC patients, statin use was associated with improved ORR (40% versus 22%, P =.04) and PFS (median 7.8 versus 3.6 months, P =.03), but no significant difference in OS was found (median 13.1 versus 10.1 months, P =.30). Multivariable analysis confirmed the correlation between statin use and better PFS and OS in MPM and better PFS in aNSCLC. In the whole cohort, high but not low/moderate-intensity statins were associated with better OS compared to no user (P =.02 and P =.59, respectively). Conclusions: Our study showed that statins are associated with better clinical outcome in MPM and aNSCLC patients treated with PD-1 inhibitors in an intensity-dependent manner