Editing Macrophage (section)

=== Cancer therapy ===
Experimental studies indicate that macrophages can affect all therapeutic modalities, including [[surgery]], [[chemotherapy]], [[radiotherapy]], [[immunotherapy]] and [[targeted therapy]].<ref name="nature.com" /><ref>{{cite journal | vauthors = Mantovani A, Allavena P | title = The interaction of anticancer therapies with tumor-associated macrophages | journal = The Journal of Experimental Medicine | volume = 212 | issue = 4 | pages = 435–445 | date = April 2015 | pmid = 25753580 | pmc = 4387285 | doi = 10.1084/jem.20150295 }}</ref><ref>{{cite journal | vauthors = De Palma M, Lewis CE | title = Macrophage regulation of tumor responses to anticancer therapies | journal = Cancer Cell | volume = 23 | issue = 3 | pages = 277–286 | date = March 2013 | pmid = 23518347 | doi = 10.1016/j.ccr.2013.02.013 | doi-access = free }}</ref> Macrophages can influence treatment outcomes both positively and negatively. Macrophages can be protective in different ways: they can remove dead tumor cells (in a process called [[phagocytosis]]) following treatments that kill these cells; they can serve as drug depots for some anticancer drugs;<ref>{{cite journal | vauthors = Miller MA, Zheng YR, Gadde S, Pfirschke C, Zope H, Engblom C, Kohler RH, Iwamoto Y, Yang KS, Askevold B, Kolishetti N, Pittet M, Lippard SJ, Farokhzad OC, Weissleder R | title = Tumour-associated macrophages act as a slow-release reservoir of nano-therapeutic Pt(IV) pro-drug | journal = Nature Communications | volume = 6 | pages = 8692 | date = October 2015 | pmid = 26503691 | pmc = 4711745 | doi = 10.1038/ncomms9692 | bibcode = 2015NatCo...6.8692M }}</ref> they can also be activated by some therapies to promote antitumor immunity.<ref>{{cite journal | vauthors = Klug F, Prakash H, Huber PE, Seibel T, Bender N, Halama N, Pfirschke C, Voss RH, Timke C, Umansky L, Klapproth K, Schäkel K, Garbi N, Jäger D, Weitz J, Schmitz-Winnenthal H, Hämmerling GJ, Beckhove P | title = Low-dose irradiation programs macrophage differentiation to an iNOS⁺/M1 phenotype that orchestrates effective T cell immunotherapy | journal = Cancer Cell | volume = 24 | issue = 5 | pages = 589–602 | date = November 2013 | pmid = 24209604 | doi = 10.1016/j.ccr.2013.09.014 | doi-access = free }}</ref> Macrophages can also be deleterious in several ways: for example they can suppress various chemotherapies,<ref>{{cite journal | vauthors = Ruffell B, Chang-Strachan D, Chan V, Rosenbusch A, Ho CM, Pryer N, Daniel D, Hwang ES, Rugo HS, Coussens LM | title = Macrophage IL-10 blocks CD8+ T cell-dependent responses to chemotherapy by suppressing IL-12 expression in intratumoral dendritic cells | journal = Cancer Cell | volume = 26 | issue = 5 | pages = 623–637 | date = November 2014 | pmid = 25446896 | pmc = 4254570 | doi = 10.1016/j.ccell.2014.09.006 }}</ref><ref>{{cite journal | vauthors = DeNardo DG, Brennan DJ, Rexhepaj E, Ruffell B, Shiao SL, Madden SF, Gallagher WM, Wadhwani N, Keil SD, Junaid SA, Rugo HS, Hwang ES, Jirström K, West BL, Coussens LM | title = Leukocyte complexity predicts breast cancer survival and functionally regulates response to chemotherapy | journal = Cancer Discovery | volume = 1 | issue = 1 | pages = 54–67 | date = June 2011 | pmid = 22039576 | pmc = 3203524 | doi = 10.1158/2159-8274.CD-10-0028 }}</ref> radiotherapies<ref>{{cite journal | vauthors = Shiao SL, Ruffell B, DeNardo DG, Faddegon BA, Park CC, Coussens LM | title = TH2-Polarized CD4(+) T Cells and Macrophages Limit Efficacy of Radiotherapy | journal = Cancer Immunology Research | volume = 3 | issue = 5 | pages = 518–525 | date = May 2015 | pmid = 25716473 | pmc = 4420686 | doi = 10.1158/2326-6066.CIR-14-0232 }}</ref><ref>{{cite journal | vauthors = Kozin SV, Kamoun WS, Huang Y, Dawson MR, Jain RK, Duda DG | title = Recruitment of myeloid but not endothelial precursor cells facilitates tumor regrowth after local irradiation | journal = Cancer Research | volume = 70 | issue = 14 | pages = 5679–5685 | date = July 2010 | pmid = 20631066 | pmc = 2918387 | doi = 10.1158/0008-5472.CAN-09-4446 }}</ref> and immunotherapies.<ref>{{cite journal | vauthors = Arlauckas SP, Garris CS, Kohler RH, Kitaoka M, Cuccarese MF, Yang KS, Miller MA, Carlson JC, Freeman GJ, Anthony RM, Weissleder R, Pittet MJ | title = In vivo imaging reveals a tumor-associated macrophage-mediated resistance pathway in anti-PD-1 therapy | journal = Science Translational Medicine | volume = 9 | issue = 389 | pages = eaal3604 | date = May 2017 | pmid = 28490665 | pmc = 5734617 | doi = 10.1126/scitranslmed.aal3604 }}</ref><ref>{{cite journal | vauthors = Zhu Y, Knolhoff BL, Meyer MA, Nywening TM, West BL, Luo J, Wang-Gillam A, Goedegebuure SP, Linehan DC, DeNardo DG | title = CSF1/CSF1R blockade reprograms tumor-infiltrating macrophages and improves response to T-cell checkpoint immunotherapy in pancreatic cancer models | journal = Cancer Research | volume = 74 | issue = 18 | pages = 5057–5069 | date = September 2014 | pmid = 25082815 | pmc = 4182950 | doi = 10.1158/0008-5472.CAN-13-3723 }}</ref> Because macrophages can regulate tumor progression, therapeutic strategies to reduce the number of these cells, or to manipulate their phenotypes, are currently being tested in cancer patients.<ref>{{cite journal | vauthors = Ries CH, Cannarile MA, Hoves S, Benz J, Wartha K, Runza V, Rey-Giraud F, Pradel LP, Feuerhake F, Klaman I, Jones T, Jucknischke U, Scheiblich S, Kaluza K, Gorr IH, Walz A, Abiraj K, Cassier PA, Sica A, Gomez-Roca C, de Visser KE, Italiano A, Le Tourneau C, Delord JP, Levitsky H, Blay JY, Rüttinger D | title = Targeting tumor-associated macrophages with anti-CSF-1R antibody reveals a strategy for cancer therapy | journal = Cancer Cell | volume = 25 | issue = 6 | pages = 846–859 | date = June 2014 | pmid = 24898549 | doi = 10.1016/j.ccr.2014.05.016 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Ruffell B, Coussens LM | title = Macrophages and therapeutic resistance in cancer | journal = Cancer Cell | volume = 27 | issue = 4 | pages = 462–472 | date = April 2015 | pmid = 25858805 | pmc = 4400235 | doi = 10.1016/j.ccell.2015.02.015 }}</ref> However, macrophages are also involved in antibody mediated cytotoxicity (ADCC) and this mechanism has been proposed to be important for certain cancer immunotherapy antibodies.<ref>{{cite journal | vauthors = Sharma N, Vacher J, Allison JP | title = TLR1/2 ligand enhances antitumor efficacy of CTLA-4 blockade by increasing intratumoral Treg depletion | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 116 | issue = 21 | pages = 10453–10462 | date = May 2019 | pmid = 31076558 | pmc = 6534983 | doi = 10.1073/pnas.1819004116 | bibcode = 2019PNAS..11610453S | doi-access = free }}</ref> Similarly, studies identified macrophages genetically engineered to express chimeric antigen receptors as promising therapeutic approach to lowering tumor burden.<ref>{{Cite journal |last1=Klichinsky |first1=Michael |last2=Ruella |first2=Marco |last3=Shestova |first3=Olga |last4=Lu |first4=Xueqing Maggie |last5=Best |first5=Andrew |last6=Zeeman |first6=Martha |last7=Schmierer |first7=Maggie |last8=Gabrusiewicz |first8=Konrad |last9=Anderson |first9=Nicholas R. |last10=Petty |first10=Nicholas E. |last11=Cummins |first11=Katherine D. |last12=Shen |first12=Feng |last13=Shan |first13=Xinhe |last14=Veliz |first14=Kimberly |last15=Blouch |first15=Kristin |date=August 2020 |title=Human chimeric antigen receptor macrophages for cancer immunotherapy |journal=Nature Biotechnology |language=en |volume=38 |issue=8 |pages=947–953 |doi=10.1038/s41587-020-0462-y |pmid=32361713 |pmc=7883632 |issn=1087-0156}}</ref>