Yes, here is what I have listed from papers, maybe we can combine everything, shorten it, simplify the language.
https://investorshangout.com/post/view?id=5486173
https://investorshangout.com/post/view?id=5494775
https://cdn.elifesciences.org/articles/43653/...653-v2.pdf
CCL5 promotes breast cancer recurrence through macrophage recruitment in residual tumors
Abstract
Over half of breast-cancer-related deaths are due to recurrence 5 or more years after initial diagnosis and treatment. This latency suggests that a population of residual tumor cells can survive treatment and persist in a dormant state for many years. The role of the microenvironment in regulating the survival and proliferation of residual cells following therapy remains unexplored. Using a conditional mouse model for Her2-driven breast cancer, we identify interactions between residual tumor cells and their microenvironment as critical for promoting tumor recurrence. Her2 downregulation leads to an inflammatory program driven by TNFα/NFκB signaling, which promotes immune cell infiltration in regressing and residual tumors. The cytokine CCL5 is elevated following Her2 downregulation and remains high in residual tumors. CCL5 promotes tumor recurrence by recruiting CCR5-expressing macrophages, which may contribute to collagen deposition in residual tumors. Blocking this TNFα-CCL5-macrophage axis may be efficacious in preventing breast cancer recurrence.
https://investorshangout.com/post/view?id=5486173
Quote:
We also have action in TaMs and MaMs, and then it could play an additional role with recurrence
Quote:so many roles Ccr5 plays in cancer’s goal metastasis. In addition to these below by Pestell, blocking Ccr5 turns MAMs from cancer promoting to cancer killing. I suspect this latest find is yet another new Ccr5 connection we will find.
Quote:
First, human breast cancer and breast cancer cell lines were shown to express CCR5 with expression patterns that are heterogeneous within the tumor, and higher cytoplasmic CCR5 staining correlated with poor prognosis.
Second, the 1668 Cancer Res; 78(7) April 1, 2018
CCR5þ-expressing human breast cancer cells within the tumor initiate tumors in mice that grow approximately 60-fold larger than CCR5 cells.
Third, CCR5 antagonists reduced the ability of basal breast cancer cells to metastasize.
Fourth, CCR5 expression correlated with the ability of breast cancer cells to form mammospheres, a surrogate assay for tumor-initiating cells. Fifth, functional analysis demonstrated endogenous CCR5 enhanced DNA repair (HDR and SSA) in response to DNA-damaging agents used in chemotherapy for breast cancer and enhanced repair in response to high dose g -irradiation and unbiased gene expression analysis of CCR5þ cells demonstrated enrichment of pathways governing DNA damage and DNA repair. Consequently, CCR5 antagonists substantially enhanced the cell killing of diverse human breast cancer cell lines in response to DNA damage– inducing chemotherapy.
Quote:Ccr5 also plays roles with the TAMs
http://cancerdiscovery.aacrjournals.org/content/6/6/571.2
The CCL5 receptor, CCR5, is not typically expressed on primary colorectal tumor cells, but was expressed by metastatic tumor cells. The production of CCL5 by T cells in the microenvironment promoted tumor cell proliferation and invasion, and increased production of matrix metalloproteinases by tumor-associated macrophages (TAM).
Read More: https://investorshangout.com/post/view?id=548...z5vNmnQj00
https://investorshangout.com/post/view?id=5494775
https://cdn.elifesciences.org/articles/43653/...653-v2.pdf
CCL5 promotes breast cancer recurrence through macrophage recruitment in residual tumors
Abstract
Over half of breast-cancer-related deaths are due to recurrence 5 or more years after initial diagnosis and treatment. This latency suggests that a population of residual tumor cells can survive treatment and persist in a dormant state for many years. The role of the microenvironment in regulating the survival and proliferation of residual cells following therapy remains unexplored. Using a conditional mouse model for Her2-driven breast cancer, we identify interactions between residual tumor cells and their microenvironment as critical for promoting tumor recurrence. Her2 downregulation leads to an inflammatory program driven by TNFα/NFκB signaling, which promotes immune cell infiltration in regressing and residual tumors. The cytokine CCL5 is elevated following Her2 downregulation and remains high in residual tumors. CCL5 promotes tumor recurrence by recruiting CCR5-expressing macrophages, which may contribute to collagen deposition in residual tumors. Blocking this TNFα-CCL5-macrophage axis may be efficacious in preventing breast cancer recurrence.
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