Here we chose to dissect the function of immunosuppressive Arg1+ TAM in an immunotherapy-responsive MC38 mouse tumor model during aPD-1 treatment. We used the syngeneic MC38 tumor model given its widespread use in immune-oncology and high macrophage content 10.

Nov 1, 2021 · We show that ARG1-targeting therapeutic vaccines were able to activate endogenous antitumor immunity in several in vivo syngeneic mouse tumor models and to modulate the cell composition of the tumor microenvironment without causing any associated side effects or systemic toxicity.

MC38 tumor cells expressed fairly low levels of Arg1 even after the uplift on day 11 (Figure 4 J). Thus, we decided to artificially modulate the arginine levels in the TME via increasing Arg1 expression in tumor cells.

We identified Arg1 + TAM–secreted PF4 as a key determinant of T H 1-T reg cell accumulation in the TME, which suppresses antitumor immunity and promotes tumor growth. Furthermore, PF4 neutralization inhibits T H 1-T reg cell polarization and suppresses tumor growth.

Feb 4, 2025 · We generated HCAR1-deficient (HCAR1 KO) and control (HCAR1 WT) colon tumor MC38 cell sublines using two single-guide RNAs (sgRNAs) and a non-targeting sgRNA, which were confirmed by...

(D) Arg1 positivity amongst several MC38 tumor immune cell populations defined by surface staining markers, pre-gated on CD45 positivity.

(G) Arg1 expression in unsorted MC38 tumor bulk samples (n=9) and isolated F4/80+tumor-infiltrating macrophages (n=3) as measured by RT-qPCR. The expression of Arg1 was evaluated relative to hypoxanthine phosphoribosyltransferase (HPRT) expression.

suppressive and tumorigenic functions and express the enzyme arginase 1 (Arg1). Methods: Here we combined high resolution intravital imaging with single cell RNA seq to uncov. r the topography and molecular profiles of immunosuppressive macrophages in mice. We further.

Apr 1, 2019 · Here, we report that anti–PD-L1 treatment favorably impacts the phenotype and function of tumor macrophages by polarizing the macrophage compartment toward a more proinflammatory phenotype. This phenotype was characterized by a decrease in Arginase-I (ARG1) expression and an increase in iNOS, MHCII, and CD40 expression.

Systemic or myeloid-specific Arg1 deletion improves antigen-induced proliferation of adoptively transferred T-cells and leads to inhibition of tumor growth. Arginase inhibitor was demonstrated to modestly inhibit tumor growth when used alone, and to potentiate antitumor effects of anti-PD-1 monoclonal antibodies and STING agonist.