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BACKGROUND: Cisplatin-based neoadjuvant chemotherapy is the standard of care for muscle invasive bladder cancer (MIBC). OBJECTIVE: To compare the efficacy and safety of the two most commonly used cisplatin-based regimens; gemcitabine, and cisplatin (GC) vs. accelerated (dose-dense: dd) or conventional methotrexate, vinblastine, adriamycin, and cisplatin (MVAC). METHODS: We searched MEDLINE, Embase, Scopus and other sources. Outcomes of interest included overall survival, downstaging to pT≤1, pathologic complete response (pCR), recurrence, and toxicity. Meta-analysis was conducted using the random-effects model. RESULTS: We identified 24 studies. Efficacy outcomes were comparable between MVAC and GC for MIBC. dd-MVAC was associated with favorable efficacy compared to GC in terms of downstaging (OR 1.45; 95%CI 1.15–1.82) and all-cause mortality at longest follow-up (OR 0.63; 95%CI 0.44–0.81). However, GC was associated with a better safety profile in terms of febrile neutropenia (OR 0.32; 95%CI 0.13–0.80), anemia (OR 0.32; 95%CI 0.18–0.54), nausea and vomiting (OR 0.27; 95%CI 0.12–0.65) compared to dd-MVAC. Compared to MVAC, patients receiving GC had an increased risk of developing grade 3–4 thrombocytopenia (OR 4.70; 95%CI 1.59–13.89) and a lower risk of nausea and vomiting (OR 0.05; 95%CI 0.01–0.31). Certainty in the estimates was very low for most outcomes. CONCLUSIONS: Efficacy and safety outcomes were comparable between MVAC and GC for MIBC. Including non-peer-reviewed studies showed higher efficacy with dd-MVAC. A phase III randomized trial comparing the two regimens is needed to guide clinical practice.

Cancer immunotherapy has revolutionized the field of oncology in recent years. Harnessing the immune system to treat cancer has led to a large growth in the number of novel immunotherapeutic strategies, including immune checkpoint inhibition, chimeric antigen receptor T-cell therapy and cancer vaccination. In this review, we will discuss the current landscape of immuno-oncology research, with a focus on elements that influence immunotherapeutic outcomes. We will also highlight recent advances in basic aspects of tumor immunology, in particular, the role of the immunosuppressive cells within the tumor microenvironment in regulating antitumor immunity. Lastly, we will discuss how the understanding of basic tumor immunology can lead to the development of new immunotherapeutic strategies.

Dendritic cells (DCs) are professional antigen-presenting cells providing costimulatory signals to adaptive immune cells. Currently, the lack of strategies to improve antigen presentation is a hindrance in tumor immunology. Despite studies focusing on antigen cross-presenting Type-1 DCs (DC1s), a study published by our lab revealed Type-2 DCs (DC2s) with significant survival across multiple human cancers. Our research group has a long-term interest in studying immune chaperone GP96, which is an essential molecular chaperone for TLRs, GARP, and other vital innate receptors. The immune-related client network of GP96 creates opportunities to unmask the roles of multiple receptors on DCs. We have generated DC-specific GP96 deficient mice and reported increased tumor-infiltrating DC2 and delayed tumor development on the spontaneous breast cancer model. However, the mechanism by which GP96 regulates DCs function is under investigation. Using different tumor models, we found that deletion of GP96 on DCs improved immune response and decreased tumor growth. However, macrophage-GP96KO mice showed a loss of benefits observed on DC-GP96KO mice. Also, differential stimulatory/inhibitory molecules on DC1 vs. DC2 were tumor-dependent. To determine the role of DC-intrinsic GP96 in T cell activation, we used in vitro antigen-cross presentation assay. We found that OT-I CD8+ T cell activation was delayed at the initial days of the co-culture with GP96KO DCs but restored in the late phase compared with WT DCs. Collectively, the results show beneficial inflammatory DC2 molecular activation, with DC1 able to cross-present antigens to CD8+ T cells. Our study indicated that targeting GP96 on DCs may contribute to shaping T cell anti-tumor immunity. Supported by grants from NIH NCI (R01:CA193939) and NIH NIAID (U01:AI125859)

Over the past year, many young creators who use the Chinese-owned social networking platform TikTok have claimed that its underlying algorithm surveils and suppresses the reach of content by Black, brown, fat, queer, and disabled creators. However, despite these algorithmic biases, these marginalized creators have continued to find new and ingenious ways to not only create but also successfully share anti-racist, anti-misogynistic, LGBTQIA+supportive, and body-positive content on the platform. Using this tension, this essay engages visual content analysis and critical technocultural discourse analysis to examine the innovative ways marginalized creators employ TikTok’s various medium and technological affordances to evade algorithmic surveillance and oppression. Building on Simone Browne’s concept of dark sousveillance, I theorize these practices as acts of digital dark sousveillance, defined within the essay as the use of digital tools to enact surveillance subversion, obfuscation, inversion while operating within systems of racializing surveillance.