%0 Journal Article
%T Myeloid-targeted immunotherapies act in synergy to induce inflammation and antitumor immunity
%A Alexra L.
%A Alexra L. Kuhlmann
%A Amezquita
%A Andr¨¦s R.
%A Andr¨¦s R. Mu£¿oz-Rojas
%A Bosenberg
%A Curtis J.
%A Curtis J. Perry
%A Damsky
%A Du
%A Durga
%A Durga Thakral
%A Jake Xiao
%A Jake Xiao Wang
%A Joel W.
%A Joel W. Sher
%A Kaech
%A Kathryn Miller-Jensen
%A Katrina M.
%A Katrina M. Meeth
%A Kellman
%A Kuhlmann
%A Laura N.
%A Laura N. Kellman
%A Marcus
%A Marcus Bosenberg
%A Meeth
%A Mu£¿oz-Rojas
%A Perry
%A Robert A.
%A Robert A. Amezquita
%A Sher
%A Susan M.
%A Susan M. Kaech
%A Thakral
%A Victor Y.
%A Victor Y. Du
%A Wang
%A William
%A William Damsky
%J JEM | The Journal of Experimental Medicine
%D 2018
%R 10.1084/jem.20171435
%X Eliciting effective antitumor immune responses in patients who fail checkpoint inhibitor therapy is a critical challenge in cancer immunotherapy, and in such patients, tumor-associated myeloid cells and macrophages (TAMs) are promising therapeutic targets. We demonstrate in an autochthonous, poorly immunogenic mouse model of melanoma that combination therapy with an agonistic anti-CD40 mAb and CSF-1R inhibitor potently suppressed tumor growth. Microwell assays to measure multiplex protein secretion by single cells identified that untreated tumors have distinct TAM subpopulations secreting MMP9 or cosecreting CCL17/22, characteristic of an M2-like state. Combination therapy reduced the frequency of these subsets, while simultaneously inducing a separate polyfunctional inflammatory TAM subset cosecreting TNF-¦Á, IL-6, and IL-12. Tumor suppression by this combined therapy was partially dependent on T cells, and on TNF-¦Á and IFN-¦Ã. Together, this study demonstrates the potential for targeting TAMs to convert a ¡°cold¡± into an ¡°inflamed¡± tumor microenvironment capable of eliciting protective T cell responses.
%U http://jem.rupress.org/content/215/3/877