M1 macrophages are classically activated, pro‑inflammatory cells that generally enhance anti‑tumor immune responses via the production of cytokines (IL‑12, TNF‑α), reactive nitrogen species (iNOS), and the expression of antigen‑presenting and costimulatory molecules (HLA‑DR, CD80, CD86).
These are macrophages activated by signals such as interferon‑γ (IFN‑γ) and microbial products (e.g., lipopolysaccharide, LPS).
Key Functional Attributes:
-Secretion of pro‑inflammatory cytokines (e.g., TNF‑α, IL‑12, IL‑1β).
-Production of reactive oxygen and nitrogen species (such as nitric oxide via inducible nitric oxide synthase, iNOS).
-Promotion of Th1 adaptive immune responses, thereby enhancing anti‑tumor immunity.
Role in Cancer:
-In the tumor microenvironment, M1 macrophages generally are considered “anti‑tumoral” since they can mediate tumor cell killing, stimulate immune responses, and inhibit tumor progression.
-However, the outcome can be context‑dependent because the balance between M1 and M2 (alternatively activated, generally pro‑tumoral) macrophages, along with other immune cells, influences the eventual prognosis.
Polarized:
– M1-polarized macrophages produce pro-inflammatory cytokines (e.g., TNF-α, IL-1β, IL-6, and IL-12) and generate reactive oxygen and nitrogen species.
– In the tumor microenvironment, the balance between M1 (pro-inflammatory, anti-tumor) and M2 (anti-inflammatory, pro-tumor) macrophages critically shapes tumor progression.
– A predominantly M1-polarized environment is generally considered to be more hostile to tumor growth, whereas M2 polarization is linked to immune suppression, tissue remodeling, and tumor progression.
• M1 polarization represents a pro-inflammatory, anti-tumor state of macrophage activation characterized by robust production of cytokines and reactive species that promote tumor cell killing and support adaptive immunity.
• Elevated levels of M1-polarized macrophages or a favorable M1/M2 ratio in the tumor microenvironment are generally associated with improved clinical outcomes and serve as potential prognostic indicators in a range of cancers.
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