Are intracellular bacteria hallmarks for human tumors?
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e intracellular bacteria hallmarks for human tumors? *
Hongquan Zhang
Peking University International Cancer Institute, Beijing 100191, China Received July 21, 2020; accepted August 10, 2020; published online August 17, 2020
Citation:
Zhang, H. (2020). Are intracellular bacteria hallmarks for human tumors? Sci China Life Sci 63, https://doi.org/10.1007/s11427-020-1793-0
There are ten major characteristics that are used to differentiate cancer from normal cells and tissue (Hanahan and Weinberg, 2011); detection of bacterial species associated with cancer cells is not included among these characteristics, and at first glance this might seem to be irrelevant. The existence of bacterial cells within tumors was first reported over a century ago; however, to this day, little is known about the relationship between bacterial species, neoplasia, and neoplastic disease. Several years ago, Dr. Leore Geller working in the laboratory of Dr. Ravid Straussman at the Department of Molecular Cell Biology at the Weizmann Institute of Science in Israel discovered that bacteria associated with colon cancer can mediate its resistance to the chemotherapeutic drug gemcitabine (Geller et al., 2017). This led everyone to wonder whether specific bacteria associated with cancer cells might be regarded as a unique hallmark for cancer. In response to this question, Dr. Deborah Nejman from the Straussman group recently reported that the human tumor microbiome includes tumor typespecific intracellular bacteria (Nejman et al., 2020; Atreya and Turnbaugh, 2020). Sensitive methods are required to characterize the bacterial species associated with specific tumors; among the challenges, one needs to develop a means to detect small populations of bacteria while eliminating any possibility of external contamination. As such, rather than isolating intact bacteria cells, sensitive and rapid methods were developed that target bacterial 16S ribosomal genes by quantitative PCR and sequencing. Using this method, Nejman et al. identified and quantified bacteria from >1000 different tu-
mors, including those from breast, lung, ovary, pancreas, melanoma, bone, and brain. Experimental controls included 516 normal tissues sampled from adjacent sites (Nejman et al., 2020). Nejman et al. reported that the microbiomes were both distinct and tumor-specific (Nejman et al., 2020). For example, their studies revealed that breast cancers maintain a particularly rich and diverse microbiome. Interestingly, some of the bacteria remained alive and could be grown directly in human breast tumor tissue. Electron microscopic visualization of these bacteria revealed that these species are localized largely intracellularly at sites adjacent to the cell nucleus. Bacteria were found both inside cancer cells and also within tumor-associated immune cells. As such, some of these bacteria may enhance anti-cancer immune responses while others may promote immunosuppression. These findings may be particularly relevant to our understanding of tumor-specific responses to immunotherapy.
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