Primary tumor-induced immunity eradicates disseminated tumor cells in syngeneic mouse model

WOS: 000462721900029PubMed ID: 30926774Although clinically apparent metastasis is associated with late stages of cancer development, micro-metastatic dissemination may be an early event. However, the fate of these early disseminated tumor cells (DTC) remains elusive. We show that despite their capacity to disseminate into secondary organs, 4T1 tumor models develop overt metastasis while EMT6-tumor bearing mice clear DTCs shed from primary tumors as well as those introduced by intravenous (IV) injection. Following the surgical resection of primary EMT6 tumors, mice do not develop detectable metastasis and reject IV-injected tumor cells. In contrast, these cells readily grow and metastasize in immuno-deficient athymic or Rag2(-/- )mice, an effect mimicked by CD8(+) T-cell depletion in immunocompetent mice. Furthermore, recombinant G-CSF or adoptive transfer of granulocytic-MDSCs isolated from 4T1 tumor-bearing mice, induce metastasis by suppressing CD8(+) T-cells in EMT6-primed mice. Our studies support the concept of immune surveillance providing molecular insights into the immune mechanisms during tumor progression.Georgia Cancer Center; Forbes Institute research fund; Bridge Fund by Augusta University Research Inc.; American Cancer Society Institutional fundWe gratefully acknowledge the generous help from Flow Cytometry, Genomics Core facilities, and Labaratory of Animal Services. We thank Drs. Rafi Ahmed and Paulo C. Rodriguez for insightful discussions and comments, Dr. Iskander Asm for for helping with and training of our staff on the tail vein injections. This work was supported by start up funds to H.K. by Georgia Cancer Center. Additional research fundings to H.K. provided by American Cancer Society Institutional fund, Forbes Institute research fund, and Bridge Fund by Augusta University Research Inc

Therapeutic utility of immunosuppressive TREM2+macrophages: An important step forward in potentiating the immune checkpoint inhibitors

In a recent article published in Cell, Molgora et al.1 reported that asubset of tumor-infiltrating macrophages with TREM2 expressioncreates an immunosuppressive microenvironment that promotestumor growth while suppressing anti-tumor immune responses.Targeting these TREM2+ macrophages via genetic ablation of thegene or specific antibodies against the protein reduces tumorgrowth in animal models; however, it further attenuates tumorgrowth when combined with immune checkpoint inhibitors (ICI)by promoting the expression of immunostimulatory molecules.Georgia Cancer Center startup fund ; American Cancer Society ; Bridge Fund by Augusta University Research Inc. ; Forbes Institute fund ; Evans County CARES fun