<> "The repository administrator has not yet configured an RDF license."^^ . <> . . "Chronic chromosome instability induced by Plk1 results in immune suppression in breast cancer"^^ . "Chromosomal instability (CIN), the failure of cells to segregate chromosomes correctly during\r\ncell division, is a typical feature of solid and hematopoietic tumors. By fostering intratumor\r\nheterogeneity and facilitating therapy resistance CIN aids in the growth of tumors. Natural killer\r\n(NK) cells have been shown to recognize and destroy cells with complex karyotypes in in vitro\r\nexperiments. Contrarily, immunosuppressive phenotype has also been noted in human\r\nmalignancies with high levels of CIN. However, which CIN-associated genetic characteristics\r\ninfluence immune recognition during tumor progression still remains to be elucidated. Previous\r\nresearch from our group demonstrated that overexpression of Polo-like kinase 1 (Plk1) in Her2-\r\npositive mammary tumors, resulted in increased CIN levels along with a delay in tumor\r\ninitiation. Using the same mouse model, I demonstrate that Her2-Plk1 tumors induce a\r\nsenescence-associated secretory phenotype (SASP) and mediate immune evasion by\r\nupregulating PD-L1 and CD206 and inducing non-cell-autonomous NF-kB signaling (RELB).\r\nImmune cells from early-stage induced mammary glands were sequenced and the results\r\ndisclosed the presence of Arg1+ macrophages with EMT signatures, NK cells (CD11b–CD27+)\r\nwith reduced effector capabilities along with increased infiltration of resting regulatory T cells\r\nduring development of Her2-Plk1 tumors compared to tumors with low CIN. Thus, immune\r\nmodulation in tumors possessing high CIN happens very early during tumor development with\r\nmultiple arms of the immune system playing an important role. We further corroborate similar\r\nfindings in human breast tumors expressing high levels of PLK1 and find upregulation of gene\r\nsets associated with SASP, NF-kB signaling and immune suppression. In conclusion, the\r\nresults presented from in vivo experiments aid in understanding the interaction between\r\ndifferent levels of CIN and the immune system. The study also highlights the need for novel\r\nadjuvant therapies such as anti-PDL1 or RELB inhibition in the context of chromosomally\r\nunstable tumors expressing PLK1"^^ . "2023" . . . . . . . "Sridhar"^^ . "Kandala"^^ . "Sridhar Kandala"^^ . . . . . . "Chronic chromosome instability induced by Plk1 results in immune suppression in breast cancer (Other)"^^ . . . . . . "lightbox.jpg"^^ . . . "Chronic chromosome instability induced by Plk1 results in immune suppression in breast cancer (Other)"^^ . . . . . . "indexcodes.txt"^^ . . . "Chronic chromosome instability induced by Plk1 results in immune suppression in breast cancer (PDF)"^^ . . . "Sridhar_thesis.pdf"^^ . . . "Chronic chromosome instability induced by Plk1 results in immune suppression in breast cancer (Other)"^^ . . . . . . "preview.jpg"^^ . . . "Chronic chromosome instability induced by Plk1 results in immune suppression in breast cancer (Other)"^^ . . . . . . "medium.jpg"^^ . . . "Chronic chromosome instability induced by Plk1 results in immune suppression in breast cancer (Other)"^^ . . . . . . "small.jpg"^^ . . "HTML Summary of #33160 \n\nChronic chromosome instability induced by Plk1 results in immune suppression in breast cancer\n\n" . "text/html" . . . "570 Biowissenschaften, Biologie"@de . "570 Life sciences"@en . .