{"id":915,"date":"2020-08-26T09:32:18","date_gmt":"2020-08-26T09:32:18","guid":{"rendered":"https:\/\/clinlabint.3wstaging.nl\/cancers-gene-determined-immune-landscape-dictates-progression-of-prostate-tumours\/"},"modified":"2021-01-08T11:08:52","modified_gmt":"2021-01-08T11:08:52","slug":"cancers-gene-determined-immune-landscape-dictates-progression-of-prostate-tumours","status":"publish","type":"post","link":"https:\/\/clinlabint.com\/cancers-gene-determined-immune-landscape-dictates-progression-of-prostate-tumours\/","title":{"rendered":"Cancer\u2019s gene-determined \u201cimmune landscape\u201d dictates progression of prostate tumours"},"content":{"rendered":"

The field of immunotherapy \u2013 the harnessing of patients\u2019 own immune systems to fend off cancer \u2013 is revolutionizing cancer treatment today. However, clinical trials often show marked improvements in only small subsets of patients, suggesting that as-yet unidentified variations among tumours result in distinct paths of disease progression and response to therapy.<\/span>
\nNow, researchers at the Cancer Center at Beth Israel Deaconess Medical Center (BIDMC) have demonstrated that genetic variations driving prostate cancer determine the composition of the immune cells that have been found to infiltrate primary prostate tumours. These immune cells, in turn, dictate tumour progression and response to treatment. The data suggest that profiling patients\u2019 tumours based on this new information could lead to more successful clinical trials and tailored therapies for patients.<\/span>
\n\u201cWe observed that specific genetic events resulted in striking differences in the composition of immune cells present in and around the tumour \u2013 results with important therapeutic implications,\u201d said senior author Pier Paolo Pandolfi, MD, PhD, Director of the Cancer Center and Cancer Research Institute at BIDMC. \u201cOur data may be especially relevant for tailoring immunological therapies and for identifying responsive-patient population.\u201d<\/span>
\nThe third leading cause of cancer-related death in U.S. men, prostate cancer, is linked to a number of diverse genetic mutations that drive the disease. For example, the loss of the tumour suppressor gene PTEN is a frequent event in prostate cancer and is well known to promote the disease in combinations with a plethora of other mutations. Researchers also know that the tumour\u2019s microenvironment \u2013 the blood vessels, immune cells, signalling molecules and other factors that surround the tumour \u2013 plays an important role in tumour progression and response to therapy.<\/span>
\nPandolfi\u2019s team \u2013 including lead author, Marco Bezzi, a post-doctoral fellow in Pandolfi\u2019s lab \u2013 engineered mice models to represent four distinct known genetic variations of human prostate cancer. The models lacked either Pten alone or in combination with other genetic alterations known to drive the disease. When the team analysed the tumours from these mice, they saw profound differences in the types and relative numbers of the immune cells that had accumulated in and around the tumour, what they call the tumours\u2019 \u201cimmune landscape\u201d.<\/span>
\nFor example, specific immune landscapes tumours from the genetic model lacking both Pten and the tumour suppressor gene called Trp53 demonstrated an increased accumulation of myeloid cells, the immune cells that mediate immunosuppression. In stark contrast, tumours from the genetic model lacking Pten and a different tumour suppressor gene called PML lacked intratumoral immune infiltration; that is, the researchers observed no immune cells at all in these tumours, which the scientists dubbed \u201ccold,\u201d or \u201cimmune-deserts.\u201d All four mouse models analysed presented very distinctive immune landscapes and these differences were maintained and exacerbated over time.<\/span>
\nThe research team also demonstrated that these differences in immune cell composition were directly dictated by the tumours themselves because of their genetic variations. Different tumours, they observed, secreted distinct chemical attractants, which in turn recruited \u2013 or didn\u2019t recruit, in the case of the immune-desert tumours \u2013 different immune cell types into the tumour. Pandolfi and colleagues further demonstrated that these differences hold true in human prostate cancer. Critically, the immune cells recruited to the tumours were found to be essential in supporting the growth and progression of these tumours.<\/span>
\n\u201cWe observed that when present, these infiltrating immune cells were required for the tumour to thrive and found therapies to block their recruitment to be effective,\u201d said Bezzi. \u201cOn the other hand, the cancer genotype characterized by the so-called \u2018immune desert\u2019 phenotype, did not respond to such therapies. On this basis, we can predict the tumour response to immunotherapies and tailor treatment modalities to effectively impact tumors that are otherwise extremely aggressive,\u201d he said.  <\/span>
\nThus, because immune cells interact with and also affect tumour response to therapy, these findings may be especially relevant for the development of more precise and effective combinations of immunotherapies and targeted therapies on the basis of the cancer genetic makeup.<\/span>
\nBeth Israel Deaconess Medical Centerwww.bidmc.org\/News\/PRLandingPage\/2018\/January\/Pandolfi-Bezzi.aspx<\/link><\/span><\/p>\n","protected":false},"excerpt":{"rendered":"

The field of immunotherapy \u2013 the harnessing of patients\u2019 own immune systems to fend off cancer \u2013 is revolutionizing cancer treatment today. However, clinical trials often show marked improvements in only small subsets of patients, suggesting that as-yet unidentified variations among tumours result in distinct paths of disease progression and response to therapy. Now, researchers […]<\/p>\n","protected":false},"author":2,"featured_media":0,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_monsterinsights_skip_tracking":false,"_monsterinsights_sitenote_active":false,"_monsterinsights_sitenote_note":"","_monsterinsights_sitenote_category":0,"footnotes":""},"categories":[35],"tags":[],"_links":{"self":[{"href":"https:\/\/clinlabint.com\/wp-json\/wp\/v2\/posts\/915"}],"collection":[{"href":"https:\/\/clinlabint.com\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/clinlabint.com\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/clinlabint.com\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/clinlabint.com\/wp-json\/wp\/v2\/comments?post=915"}],"version-history":[{"count":0,"href":"https:\/\/clinlabint.com\/wp-json\/wp\/v2\/posts\/915\/revisions"}],"wp:attachment":[{"href":"https:\/\/clinlabint.com\/wp-json\/wp\/v2\/media?parent=915"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/clinlabint.com\/wp-json\/wp\/v2\/categories?post=915"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/clinlabint.com\/wp-json\/wp\/v2\/tags?post=915"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}