Lilie L. Lin

Tumor microbiota can produce active metabolites that affect cancer and immune cell signaling, metabolism, and proliferation. Here, we explore tumor and gut microbiome features that affect chemoradiation response in patients with cervical cancer using a combined approach of deep microbiome sequencing, targeted bacterial culture, and in vitro assays. We identify that an obligate L-lactate-producing lactic acid bacterium found in tumors, Lactobacillus iners, is associated with decreased survival in patients, induces chemotherapy and radiation resistance in cervical cancer cells, and leads to metabolic rewiring, or alterations in multiple metabolic pathways, in tumors. Genomically similar L-lactate-producing lactic acid bacteria commensal to other body sites are also significantly associated with survival in colorectal, lung, head and neck, and skin cancers. Our findings demonstrate that lactic acid bacteria in the tumor microenvironment can alter tumor metabolism and lactate signaling pathways, causing therapeutic resistance. Lactic acid bacteria could be promising therapeutic targets across cancer types.

Purpose Cervical cancer is the leading cause of cancer death among the 20 million women with HIV worldwide. We sought to determine whether HIV infection affected survival in women with invasive cervical cancer. Patients and Methods We enrolled sequential patients with cervical cancer in Botswana from 2010 to 2015. Standard treatment included external beam radiation and brachytherapy with concurrent cisplatin chemotherapy. The effect of HIV on survival was estimated by using an inverse probability weighted marginal Cox model. Results A total of 348 women with cervical cancer were enrolled, including 231 (66.4%) with HIV and 96 (27.6%) without HIV. The majority (189 [81.8%]) of women with HIV received antiretroviral therapy before cancer diagnosis. The median CD4 cell count for women with HIV was 397 (interquartile range, 264 to 555). After a median follow-up of 19.7 months, 117 (50.7%) women with HIV and 40 (41.7%) without HIV died. One death was attributed to HIV and the remaining to cancer. Three-year survival for the women with HIV was 35% (95% CI, 27% to 44%) and 48% (95% CI, 35% to 60%) for those without HIV. In an adjusted analysis, HIV infection significantly increased the risk for death among all women (hazard ratio, 1.95; 95% CI, 1.20 to 3.17) and in the subset that received guideline-concordant curative treatment (hazard ratio, 2.63; 95% CI, 1.05 to 6.55). The adverse effect of HIV on survival was greater for women with a more-limited stage cancer ( P = .035), those treated with curative intent ( P = .003), and those with a lower CD4 cell count ( P = .036). Advanced stage and poor treatment completion contributed to high mortality overall. Conclusion In the context of good access to and use of antiretroviral treatment in Botswana, HIV infection significantly decreases cervical cancer survival.

OBJECTIVES: The cancer burden in low- and middle-income countries (LMIC) is substantial. The purpose of this study was to identify and describe country and region-specific patterns of radiotherapy (RT) facilities in LMIC. METHODS: A systematic review of the literature was undertaken. A search strategy was developed to include articles on radiation capacity in LMIC from the following databases: PubMed, Embase, CINAHL Plus, Global Health, and the Latin American and Caribbean System on Health Sciences Information. Searches included all literature up to April 2013. RESULTS: A total of 49 articles were included in the review. Studies reviewed were divided into one of four regions: Africa, Asia, Eastern Europe, and South America. The African continent has the least amount of resources for RT. Furthermore, a wide disparity exists, as 60% of all machines on the continent are concentrated in Egypt and South Africa while 29 countries in Africa are still lacking any RT resource. A significant heterogeneity also exists across Southeast Asia despite a threefold increase in megavoltage teletherapy machines from 1976 to 1999, which corresponds with a rise in economic status. In LMIC of the Americas, only Uruguay met the International Atomic Energy Agency recommendations of 4 MV/million population, whereas Bolivia and Venezuela had the most radiation oncologists (>1 per 1000 new cancer cases). The main concern with the review of RT resources in Eastern Europe was the lack of data. CONCLUSION: There is a dearth of publications on RT therapy infrastructure in LMIC. However, based on limited published data, availability of RT resources reflects the countries' economic status. The challenges to delivering radiation in the discussed regions are multidimensional and include lack of physical resources, lack of human personnel, and lack of data. Furthermore, access to existing RT and affordability of care remains a large problem.