Macrophages within solid tumors and metastatic sites are heterogenous populations with different developmental origins and substantially contribute to tumor progression. A number of tumor-promoting phenotypes associated with both tumor- and metastasis-associated macrophages are similar to innate programs of embryonic-derived tissue-resident macrophages. In contrast to recruited macrophages originating from marrow precursors, tissue-resident macrophages are seeded before birth and function to coordinate tissue remodeling and maintain tissue integrity and homeostasis. Both recruited and tissue-resident macrophage populations contribute to tumor growth and metastasis and are important mediators of resistance to chemotherapy, radiation therapy, and immune checkpoint blockade. Thus, targeting various macrophage populations and their tumor-promoting phenotypes holds therapeutic promise. Here, we discuss various macrophage populations as regulators of tumor progression, immunity, and immunotherapy. We provide an overview of macrophage targeting strategies, including therapeutics designed to induce macrophage depletion, impair recruitment, and induce repolarization. We also provide a perspective on the therapeutic potential for macrophage-specific acquisition of trained immunity as an anti-cancer agent and discuss the therapeutic potential of exploiting macrophages and their traits to reduce tumor burden.

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Objectives: As the COVID-19 pandemic persisted into the 2020 to 2021 academic year, there was a continued effect on graduate medical education trainees and graduating trainee job attainment. Our survey aims to investigate how the pandemic has continued to affect job search and attainment for pediatric gastroenterology fellows as well as to re-evaluate the pandemic’s impact on pediatric gastroenterology fellow educational experiences. Methods: An anonymous survey was distributed to all North American pediatric gastroenterology fellows from May to June 2021. Survey questions included topics related to job search and fellowship training and were tailored to respondent year of training. Results: Of 453 pediatric gastroenterology fellows in the 2020 to 2021 academic year, 158 fellows (35%) responded to the survey. Of graduating fellow respondents with job contracts, 74% reported willingness to make compromises in their job search, 76% reported accepting academic positions that were primary clinical, and 42% estimated staying at their accepted job for less than 5 years. When asked about the impact of COVID-19 on various aspects of fellowship education, a negative impact was reported in the following areas: 76% in research, 94% in clinical experience, 73% in procedural skills, and 84% in didactics. Conclusion: The COVID-19 pandemic continues to make a significant impact on pediatric gastroenterology fellowship education and the job attainment process. Regarding accepted job positions, we found substantial willingness to compromise, a shorter duration to stay at the job than expected, and minimal research focus. This raises concern regarding job preparedness and satisfaction as fellows complete their medical training.

BACKGROUND: The mode of action of Bacillus Calmette-Guérin (BCG) in the treatment of patients with non-muscle invasive bladder cancer (NMIBC) is incompletely understood, but recent studies support an association between BCG-induced trained immunity in circulating monocytes and disease-free survival. OBJECTIVE: We compared epigenetic profiles in monocytes from NMIBC patients with early disease recurrence with those from recurrence-free patients. METHODS: We conducted chromatin immunoprecipitation and DNA sequencing (ChIP-seq) on monocytes from seven patients treated with BCG (four with early recurrences and three recurrence-free after one year) to determine genome-wide distribution and abundance of histone 3 lysine 4 trimethylation (H3K4me3) prior to and after five weeks of induction therapy. RESULTS: Genome-wide H3K4me3 profiles before or after BCG induction distinguished patients with early recurrences from those remaining recurrence-free. Furthermore, H3K4me3 levels at genes involved in specific pathways were increased in the recurrence-free group. Independent quantification showed increased H3K4me3 levels in elements of the Wnt and AMPK signaling pathways in the recurrence-free group before BCG initiation, while elements of the MAPK showed increased levels after five weeks of induction in the same group. Validation of these genes on an independent cohort of four additional patients that remained recurrence-free after one year and three with early recurrences revealed consistent increases in H3K4me3 levels associated with MAPK pathway genes after five weeks of BCG treatment in the recurrence-free group. CONCLUSIONS: Recurrence-free survival following BCG immunotherapy for NMIBC is associated with the accumulation of H3K4me3 at specific gene loci and could lead to identification of prognostic biomarkers.