Researchers discover immune cell “hubs” hiding in tumors

Credit: Joshua Pirl, Vjola Jorgji, Linda Nieman, Jonathan Chen. Source: Pelka, Hofree, Chen et al. Cell. 2021 In a subset of human colorectal tumors, immune cells such as activated and potentially tumor-reactive T cells (white, green, and magenta) are organized into “hubs” around malignant cells (blue) expressing molecules (yellow) that attract immune cells.

A team of researchers has gained new insight into how tumors are organized. They have discovered that immune cells in some human colorectal tumors gather together in clusters, like soldiers mobilizing in formation. By using a unique combination of single-cell profiling and imaging technologies, along with newly developed data analysis approaches, the scientists found a level of spatial organization of cells not observed before in tumors. The findings point to networks of interacting immune cells in certain types of colorectal tumors that tend to be more readily “seen” by the immune system. This suggests that cancers containing these hubs may be more likely to respond to cancer drugs called immunotherapies, which spur the immune system to kill cancer cells.

“Complex systems such as tumors require a network of researchers with different expertise to take on the challenge of studying their cellular organization,” said co-senior author Ana Anderson, PhD, of the Brigham’s Department of Neurology. “Working with a collaborative team across multiple institutions is what allowed us to undertake this unique study and reach a new view of how immune cells are organized in tumors.”

Read more in Cell and in a Broad Institute news story.


Study of Co-Infections in the Female Genital Tract Uncovers New Molecular Mechanism for How Pathogens Evade the Immune System

The molecular synergy between bacteria, endosymbiont virus and protozoan parasites may help sexually transmittable pathogens evade the human host, a new Brigham study concludes. Using the HIV Epidemiology Research Study (HERS), which started in 1992, the researchers assessed participants after each of their incident Trichomonas vaginalis (TV) infection visits. TV is the most common sexually-transmitted pathogen, aside from human papillomavirus (HPV) and genital herpes, and accounts for nearly half of the almost 500 million sexually transmitted infections annually. The researchers found that incident TV is associated with altered levels of galectins, a glycan-sensing family of proteins, in the cervicovaginal region, which correlates with mediators of inflammation. Virus-inhabited parasites synergized with bacterial pathogens to increase expression of selected galectins facilitating parasitic infection.

“Our study is the first report to show molecular synergisms between bacteria, endosymbiont virus and protozoan parasite evading the human host – both with clinical association and experimental proof of causality,” said Raina Fichorova, MD, PhD, of the Brigham’s Department of Obstetrics and Gynecology. “It addresses the most common and devastating infections of the female reproductive tract, including protozoan (trichomonas), viral (HPV and herpes simplex virus), and bacterial (bacterial vaginosis pathobionts key to mucosal dysbiosis). Our paper is also the first to implicate galectins in viral-protozoan-bacterial-host interaction in the female genital tract.”

Read more in Frontiers in Medicine. 

Computational Analysis Reveals Sources of Genetic Variations

A new multi-institutional study led by investigators at Harvard Medical School and the Brigham has pinpointed nine processes during which most human genetic mutations tend to arise. The work is based on an analysis of 400 million rare DNA human variants and represents one of the most comprehensive computational efforts to explore heritable genomic variations.

“Genetic mutations are a rare yet inevitable and, indeed essential, part of the development and propagation of the human species—they create genetic diversity, fuel evolution, and occasionally cause genetic diseases,” said study lead investigator Shamil Sunyaev, PhD, professor of biomedical informatics in the Blavatnik Institute at HMS and a research geneticist in the Brigham’s Division of Genetics.

Read more in Science and on the HMS News site.

Neutrophils Show Promise as New Immunotherapeutic Approach in Cancer Treatment

A Brigham study describes a method to generate immunogenic antigen presenting cells from the most abundant white blood cells in the body, neutrophils. Although T-cell based immunotherapy has shown promising results in cancer patients, it has low rates of response and can also result in serious autoimmune complications. These issues could be overcome by increasing the number of antigen-specific T-cells. The team describes how immunization with an anti-FcγRIIIB-antigen conjugate that targets neutrophils may be used to generate large quantities of highly immunogenic neutrophil-derived antigen-presenting cells that activate T cells and exhibit anti-tumorigenic properties in mouse models.

“Our paper is very timely as another recent publication in Nature Cancer (Haas et al 2021) demonstrated the importance of adequate numbers and activation of dendritic cells, the classical antigen presenting cells of the body, in cancer immunotherapy,” said Tanya Mayadas, PhD, of the Brigham’s Department of Pathology. “A method that generates potent, immunogenic antigen presenting cells from neutrophils may alone be useful to promote anti-tumor immunity and, in combination approaches, improve the effectiveness of T cell-based immunotherapies.”

Read more in Nature Communications.