Kepeng Wang, assistant professor of immunology at UConn Health, is investigating the complex relationship between cytokines and colorectal cancer.<\/p>\n
Wang\u2019s work is supported by a $1.8 million grant from the National Cancer Institute.<\/p>\n
Cytokines are a category of proteins secreted by cells. They have an important role in cell signaling. IL-17 cytokines, one family of cytokines, promote inflammation which drives the growth of tumors on the colon. This often leads to colorectal cancer.<\/p>\n
To date, the underlying mechanism explaining IL-17’s connection with colorectal cancer relies on its role in helping the tumor recruit myeloid cells, which come from bone marrow. This provides the tumor with a powerful ally to help it grow and spread throughout the body.<\/p>\n
What scientists do not yet fully understand is if IL-17 also signals regulatory T cells (Tregs). Tregs are often recruited to tumors and hinder the body\u2019s natural ability to impede tumor growth.<\/p>\n
Wang\u2019s preliminary studies show that removing IL-17 signaling on Treg cells increased colonic tumor development in mice. This demonstrated a previously unknown protective role of IL-17 in colorectal cancer, indicating its relationship with tumorigenesis and growth is more complicated than previously thought.<\/p>\n
Wang\u2019s team found that IL-17 inhibits Treg accumulation in tumors, a measure that typically indicates a grim prognosis. IL-17 also inhibits the expression of genes that facilitate Treg migration, proliferation, and their ability to suppress the immune system.<\/p>\n
Interestingly, Wang\u2019s team only observed these inhibitory effects in tumor-infiltrating Tregs and not in healthy Tregs. This suggests IL-17 engages in site-specific inhibition. Accordingly, only Tregs that infiltrate tumors express the receptors IL-17 cytokines attach to in order to initiate this cascade.<\/p>\n
When Wang stimulated Tregs with two cytokines that are abundant in the tumor environment, it led to increased production of the IL-17 receptor. This suggests when Tregs are recruited to tumors, the tumor\u2019s environment makes it more susceptible to being inhibited by IL-17.<\/p>\n
Conversely, Wang and his team found that IL-17 signals to tumor cells to reduce the expression of cytokines that signal CD8+ CTL T cells to the tumor. These T cells play an important role in immunity and tumor surveillance. These cytokines are known as CXCL9 and CXCL10.<\/p>\n
This means IL-17 inhibits Tregs that would otherwise suppress cancer immunosurveillance while also inhibiting the attraction of T cells that would perform this function. These findings illuminate the complicated role of IL-17 in colorectal cancer and showcase the need for further investigation.<\/p>\n
Now, Wang is looking to further his previous work and clarify IL-17’s role in colorectal cancer.<\/p>\n
Wang will describe how, exactly, IL-17 mediates the direct inhibition of Tregs in colorectal tumors as well as identify the underlying molecular mechanisms of this process. Wang will then interrogate how IL-17 inhibits T cell attraction through the regulation of CXCL9 and CXCL10.<\/p>\n
Ultimately, Wang will test the importance of these interactions and effects in colorectal tumor development and therapies.<\/p>\n
\u201cThese investigations will provide new insights into the mechanisms by which IL-17 impacts colorectal tumorigenesis, as well as guide the invention and use of novel therapies for the treatment of colorectal,\u201d Wang says.<\/p>\n
For example, understanding how IL-17 inhibits CD8+ CTL T cell attraction to tumors could mean adding already available IL-17 antibodies to cancer immunotherapy regimes would improve patient outcomes. While, if a tumor has abundant IL-17 and Tregs, researchers and clinicians could know that using IL-17 antibodies may have an adverse effect for the patient since IL-17 is performing a protective role in this case.<\/p>\n
This work can help provide a pathway toward more precise treatments for colorectal cancer patients.<\/p>\n
Wang holds a Ph.D. in biochemistry from Hong Kong University of Science and Technology. Wang\u2019s lab focuses on studying the role of inflammation in colorectal cancer development and therapeutic intervention.<\/em><\/p>\n Follow UConn Research on <\/em>Twitter<\/em><\/a> & <\/em>LinkedIn.<\/em><\/a><\/p>\n","protected":false},"excerpt":{"rendered":" Kepeng Wang is paving the way to better colorectal cancer treatments by interrogating the multifaceted relationship between cytokines and colon tumors. <\/p>\n","protected":false},"author":147,"featured_media":176718,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"_crdt_document":"","wds_primary_category":0,"wds_primary_series":0,"wds_primary_attribution":0,"footnotes":""},"categories":[2230,2076,1868,179],"tags":[],"magazine-issues":[],"coauthors":[2277],"class_list":["post-176700","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-cancer","category-research","category-meds","category-uconn-health"],"pp_statuses_selecting_workflow":false,"pp_workflow_action":"current","pp_status_selection":"publish","acf":[],"publishpress_future_action":{"enabled":false,"date":"2026-05-08 11:31:08","action":"change-status","newStatus":"draft","terms":[],"taxonomy":"category","extraData":[]},"publishpress_future_workflow_manual_trigger":{"enabledWorkflows":[]},"_links":{"self":[{"href":"https:\/\/today.uconn.edu\/wp-rest\/wp\/v2\/posts\/176700","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/today.uconn.edu\/wp-rest\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/today.uconn.edu\/wp-rest\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/today.uconn.edu\/wp-rest\/wp\/v2\/users\/147"}],"replies":[{"embeddable":true,"href":"https:\/\/today.uconn.edu\/wp-rest\/wp\/v2\/comments?post=176700"}],"version-history":[{"count":2,"href":"https:\/\/today.uconn.edu\/wp-rest\/wp\/v2\/posts\/176700\/revisions"}],"predecessor-version":[{"id":178370,"href":"https:\/\/today.uconn.edu\/wp-rest\/wp\/v2\/posts\/176700\/revisions\/178370"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/today.uconn.edu\/wp-rest\/wp\/v2\/media\/176718"}],"wp:attachment":[{"href":"https:\/\/today.uconn.edu\/wp-rest\/wp\/v2\/media?parent=176700"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/today.uconn.edu\/wp-rest\/wp\/v2\/categories?post=176700"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/today.uconn.edu\/wp-rest\/wp\/v2\/tags?post=176700"},{"taxonomy":"magazine-issue","embeddable":true,"href":"https:\/\/today.uconn.edu\/wp-rest\/wp\/v2\/magazine-issues?post=176700"},{"taxonomy":"author","embeddable":true,"href":"https:\/\/today.uconn.edu\/wp-rest\/wp\/v2\/coauthors?post=176700"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}