The microbiome has clearly been established as a cutting-edge field in tumor immunology and immunotherapy. Growing evidence supports the role of the microbiome in immune surveillance, self-tolerance, and response to immune checkpoint inhibitors such as anti PD-L1 and CTLA-4 blockade (1–6). Moreover, recent studies including those using fecal microbial transplantation (FMT) have demonstrated that response to checkpoint immunotherapies may be conferred or eliminated through gut microbiome modulation (7, 8). Consequently, studies evaluating microbiota-host immune and metabolic interactions remain an area of high impact research. While observations in murine models have highlighted the importance of the microbiome in response to therapy, we lack sufficient understanding of the exact mechanisms underlying these interactions. Furthermore, mouse and human gut microbiome composition may be too dissimilar for discovery of all relevant gut microbial biomarkers. Multiple cancers in dogs, including lymphoma, high grade gliomas, melanomas and osteosarcoma (OSA) closely resemble their human analogues, particularly in regard to metastasis, disease recurrence and response to treatment. Importantly, dogs with these spontaneous cancers also have intact immune systems, suggesting that microbiome analyses in these subjects may provide high yield information, especially in the setting of novel immunotherapy regimens which are currently expanding rapidly in canine comparative oncology (9, 10). Additionally, as onco-microbiotic therapies are developed to modify gut microbiomes for maximal responsiveness, large animal models with intact immune systems will be useful for trialing interventions and monitoring adverse events. Together, pre-clinical mechanistic studies and large animal trials can help fully unlock the potential of the microbiome as a diagnostic and therapeutic target in cancer.

BackgroundGroundbreaking studies have linked the gut microbiome with immune homeostasis and antitumor immune responses. Mounting evidence has also demonstrated an intratumoral microbiome, including in soft tissue sarcomas (STS), although detailed characterization of the STS intratumoral microbiome is limited. We sought to characterize the intratumoral microbiome in patients with STS undergoing preoperative radiotherapy and surgery, hypothesizing the presence of a distinct intratumoral microbiome with potentially clinically significant microbial signatures.MethodsWe prospectively obtained tumor and stool samples from adult patients with non-metastatic STS using a strict sterile collection protocol to minimize contamination. Metagenomic classification was used to estimate abundance using genus and species taxonomic levels across all classified organisms, and data were analyzed with respect to clinicopathologic factors.ResultsFifteen patients were enrolled. Most tumors were located at an extremity (67%) and were histologic grade 3 (87%). 40% were well-differentiated/dedifferentiated liposarcoma histology. With a median follow-up of 24 months, 4 (27%) patients developed metastases, and 3 (20%) died. Despite overwhelming human DNA (>99%) intratumorally, we detected a small but consistent proportion of bacterial DNA (0.02–0.03%) in all tumors, includingProteobacteria, Bacteroidetes,andFirmicutes, as well as viral species. In the tumor microenvironment, we observed a strong positive correlation between viral relative abundance and natural killer (NK) infiltration, and higher NK infiltration was associated with superior metastasis-free and overall survival by immunohistochemical, flow cytometry, and multiplex immunofluorescence analyses.ConclusionsWe prospectively demonstrate the presence of a distinct and measurable intratumoral microbiome in patients with STS at multiple time points. Our data suggest that the STS tumor microbiome has prognostic significance with viral relative abundance associated with NK infiltration and oncologic outcome. Additional studies are warranted to further assess the clinical impact of these findings.

Whether undocumented immigrants should or should not be systematically granted access to the benefits of kidney transplant generates significant debate. [1][2][3][4][5] Yet, little is known about undocumented immigrants' actual transplant outcomes. 1,5 Our study's aim was to perform a granular single-center analysis of our program's considerable long-term experience with a large cohort of predominantly adult undocumented immigrants to provide much needed data for public debate and policy making.

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ObjectivesComorbid psychiatric illness has been associated with worse outcomes after some major surgical procedures. We hypothesized that patients with preexisting mood disorders would have worse postoperative and oncologic outcomes after pancreatic cancer resection.MethodsThis retrospective cohort study analyzed Surveillance, Epidemiology, and End Results patients with resectable pancreatic adenocarcinoma. A preexisting mood disorder was classified if a patient was diagnosed and/or treated with medication approved for depression/anxiety within 6 months before surgery.ResultsOf 1305 patients, 16% had a preexisting mood disorder. Mood disorders had no impact on hospital length of stay (12.9 vs 13.2 days, P = 0.75), 30-day complications (26% vs 22%, P = 0.31), 30-day readmissions (26% vs 21%, P = 0.1), or mortality (30 days: 3% vs 4%, P = 0.35); only an increased 90-day readmissions rate (42% vs 31%, P = 0.001) was observed. No effect on adjuvant chemotherapy receipt (62.5% vs 69.2%, P = 0.06) or survival (24 months, 43% vs 39%, P = 0.44) was observed.ConclusionsPreexisting mood disorders influenced 90-day readmissions after pancreatic resection, but not other postoperative or oncologic outcomes. These findings suggest that affected patients should be expected to have outcomes similar to patients without mood disorders.