Chronic Inflammation and Cancer
July 8, 2026Core Framework & Diagram How Does the Tumor ‘Turn Off’ Immune Switches?
July 8, 2026
How Does the Tumor 'Turn Off' Immune Switches?
Tumors don't just evade the immune system — they actively turn off every immune 'switch'
By the Editors 1-min read
Article 68 covered tumors' five-dimensional defense system. This article focuses on the most precise dimension: how tumors actively manipulate 'immune switches.' Your immune system has two types of switches — activation switches (signals telling immune cells to launch attacks) and inhibitory switches (signals telling immune cells to stop attacking). Tumors, almost without exception, have learned to systematically turn off 'activation switches' while turning on 'inhibitory switches' — continuously telling every immune cell entering their territory 'no danger, all normal, stop attacking.'
Understanding how tumors manipulate these immune switches is understanding why immune checkpoint inhibitors work — and why next-generation immunotherapy needs to simultaneously handle more 'switches.'
KEY TAKEAWAYS
01
Tumors systematically manipulate five major immune switch categories: cell surface checkpoints (PD-L1/CTLA-4), T cell exhaustion multi-checkpoints (LAG-3/TIM-3/TIGIT), innate immune 'don't eat me' signals (CD47-SIRPα), metabolic immune anesthesia (CD39/CD73/adenosine), and secreted all-purpose immune suppression (TGF-β) — forming redundant multiple defense lines.
02
LAG-3 is the third immune checkpoint with proven clinical efficacy after CTLA-4 and PD-1: 2022 FDA approval of relatlimab+nivolumab for melanoma, extending median PFS from 4.6 to 10.1 months.
03
CD47 is a 'dual pass' strategy connecting innate and adaptive immunity: tumors simultaneously evade macrophage phagocytosis and subsequent T cell activation via CD47 upregulation. CD47 blockade re-activates macrophage phagocytosis, simultaneously triggering antigen presentation and T cell response.
04
The adenosine pathway (CD39→CD73→adenosine→A2aR) converts ATP (should activate immunity) into adenosine (immunosuppressive). A2aR antagonists combined with PD-1 inhibitors are an important exploration direction for PD-1 monotherapy non-responders.
05
TGF-β is the most comprehensive immune suppression switch: simultaneously directly suppressing CTLs, inducing Tregs, M2-TAM polarization, driving EMT, and constructing physical barriers. Local TME-targeted TGF-β blockade (bispecific PD-L1×TGF-β) is the most promising overcoming approach.
Art 78
How Does the Tumor Transform Immune Cells?
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Art 79
How Does the Tumor Exploit Stress Signals?
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