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. 2026 Jan 12;16:1731338. doi: 10.3389/fimmu.2025.1731338

Figure 1.

Diagram illustrating immune cell interactions in cancer cell death and wound healing. Cells like T_CD4+, T_CD8+, and DC' are shown with cytokines IL-2, IFNγ, and IL-12. M1 and M2 macrophages, CTLs, NK cells, and others are depicted engaging in processes like efferocytosis and releasing SPMs. Chemical environment factors such as glucose, lactate, and pH are indicated. The image also shows fibroblasts, platelets, and myofibroblasts in the context of wound healing and the extracellular matrix compound's role in cancer cell death.

Network of cellular and molecular events for tissue regeneration. Innate and adaptive immune cells cooperate to eliminate transformed cells through cytotoxic and inflammatory mechanisms. Natural killer (NK) and invariant NK (iNK) cells release perforin (PFN) and granzyme B (GzmB) to induce tumor cell death, while dendritic cells (DCs) activate CD4+ and CD8+ T cells via IL-12 signaling, leading to IL-2 and IFN-γ secretion that amplifies cytotoxic activity. Damage- and pathogen-associated molecular patterns (DAMPs and PAMPs) recruit neutrophils (N1) and M1 macrophages, which generate reactive oxygen and nitrogen species (ROS, NOS) to promote further tumor clearance. As dying cells accumulate, macrophages initiate efferocytosis and metabolic reprogramming under a microenvironment characterized by low glucose and glutamine availability, acidic pH, hypoxia, and increased lactate. This shift favors the production of specialized pro-resolving mediators (SPMs) such as lipoxins, resolvins, protectins, and maresins, and the secretion of anti-inflammatory cytokines (IL-10, TGF-β) and growth factors (VEGF, FGF). These mediators orchestrate fibroblast activation, myofibroblast differentiation, and extracellular matrix (ECM) deposition, leading to re-epithelialization and tissue repair, processes that, while essential for resolution of inflammation, may also set the stage for a regenerative or pre-neoplastic niche. Color and arrows: Black arrows indicate activation or production; red arrows indicate inhibition or depletion.