Nobel Prize Endorsed, The Tipping Point Arrives: How Treg Therapy Is Reshaping the Treatment Landscapes of Cancer and Autoimmune Diseases?

In the afternoon of October 6th (Beijing), the highly anticipated 2025 Nobel Prize in Physiology or Medicine laureates were officially announced. Mary E. Brunkow, Fred Ramsdell, and Shimon Sakaguchi were jointly honored for their pioneering research in peripheral immune tolerance. Their work spans from molecular mechanisms to cellular functions, comprehensively elucidating the key principles by which the immune system achieves “self-tolerance.” This breakthrough lays a foundational theoretical basis for treating diseases such as autoimmune diseases and cancer.

 Figure 1. Laureates of the 2025 Nobel Prize in Physiology or Medicine ^[1]

This prestigious award not only marks a milestone in immunology research but also positions Treg-based therapies as a pivotal force reshaping the treatment landscape of cancer and autoimmune disease. From breakthroughs in fundamental mechanisms to accelerated clinical translation, Treg therapy is demonstrating immense potential to reshape future treatment paradigms through its unique “bidirectional regulation” advantage.

I. Research History of Regulatory T Cells (Treg)

The research history of Treg can be divided into four phases: conceptual inception, core exploration, mechanism elucidation, and clinical application. Its journey evolved from an overlooked hypothesis to a paradigm in core immunology.

Phase I: Conceptual Inception (1970s–1980s)

● Scientists proposed the “suppressor T cell” hypothesis, suggesting certain T cells could inhibit immune responses. However, this concept was shelved due to the lack of clear markers and mechanistic evidence.

● Thymectomy in newborn mice led to severe autoimmune diseases, indirectly demonstrating that the thymus likely produces specialized T cells maintaining immune tolerance.

Phase II: Core Exploration (1990s–2000s)

● In 1995, Shimon Sakaguchi’s team identified CD4⁺ T cells highly expressing CD25 in mice and humans. Experiments confirmed that removing these cells induced autoimmune disease, while reinfusion prevented it, leading to their formal designation as “regulatory T cells (Treg).”

● In 2003, Sakaguchi's team and Rudensky's team simultaneously identified the transcription factor Foxp3 as the master regulator of Treg development and function, providing Tregs with a “molecular ID card.”

Phase III: Mechanism Elucidation (2000s–2010s)

● Clarification of Treg suppression mechanisms: Treg exert effects through multiple pathways including cell-cell contact, secretion of inhibitory factors, metabolic interference, and modulation of antigen-presenting cell function.

Phase IV: Clinical Applications (2010s–Present)

● Autoimmune Diseases and Transplantation: Attempts to treat diseases by ex vivo expansion and reinfusion of Treg.

● Cancer Therapy: Developing drugs that selectively eliminate Treg within tumors to unleash anti-cancer immunity.

The history of Treg research perfectly illustrates the scientific discovery process: from vague concepts to solid evidence, ultimately profoundly reshaping our understanding of life and disease treatment. It has also established immune balance, rather than immune attack, as the core concept of modern immunology.

II. Mechanisms of Regulatory T Cells (Treg)

The precise regulation of immune system is analogous to a sophisticated driving system. Effector T cells (Teff) act as the “accelerator,” responsible for attacking foreign invaders, while Treg cells serve as the “brakes,” maintaining immune tolerance balance—preventing the immune system from attacking its own tissues (avoiding autoimmune diseases) and curbing excessive immune activation (reducing inflammatory damage). Their mechanisms can be summarized in the following core aspects:

1. Secretion of Inhibitory Cytokines

IL-10: Potently inhibits the activation of macrophages and dendritic cells, thereby indirectly suppressing Teff.

TGF-β: Inhibits the proliferation and function of T cells and B cells, serving as a key factor in maintaining peripheral tolerance.

IL-35: A relatively newly discovered suppressive cytokine that directly inhibits the response of Teff.

2. Cell contact-dependent inhibition

CTLA-4 pathway: Treg highly express CTLA-4, which binds to CD80/CD86 on antigen-presenting cells (APCs), transmitting inhibitory signals that render APCs dysfunctional and incapable of effectively activating Teff.

Granzyme/perforin pathway: Partially activated Treg can directly kill effector immune cells by releasing granzyme and perforin, similar to cytotoxic T cells.

3. Metabolic Interference

IL-2 Deprivation: Tregs highly express high-affinity IL-2 receptors, competitively “stealing” IL-2 from the microenvironment, causing IL-2-dependent Teff to undergo apoptosis due to “starvation.”

cAMP Transfer: Transferring high levels of cyclic adenosine monophosphate (cAMP) to Teff via gap junctions, directly inhibiting their activation.

Adenosine Production: Tregs express CD39 and CD73, enabling hydrolysis of extracellular ATP/ADP into adenosine, which exerts immunosuppressive effects.

4. Modulation of Antigen-Presenting Cell Function

Downregulation of co-stimulatory molecules: Induces downregulation of CD80/CD86 expression on APC surfaces via pathways such as CTLA-4.

Induction of inhibitory molecules: Promotes APC expression of immunosuppressive enzymes like IDO.

 Figure 2. Mechanisms of Treg in Autoimmunity ^[2]

III. Reshaping Cancer Immunotherapy: From “Releasing the Brakes” to “Precision Regulation”

Within the tumor microenvironment, cancer cells recruit large numbers of Tregs to form an immunosuppressive barrier. By overexpressing molecules like CTLA-4, they suppress Teff activity, aiding tumor escape from immune clearance. Clinical data show that Treg infiltration levels in tumor tissues correlate directly with poor prognosis, treatment resistance, and high recurrence rates across multiple cancers. Thus, Treg therapeutic strategies in oncology focus on selectively weakening Treg function within the tumor microenvironment.

Strategy 1: Targeted Elimination of Tregs in the Tumor Microenvironment

● Target: CCR8. Research reveals that tumor-infiltrating Treg specifically overexpress the chemokine receptor CCR8. Antibodies targeting CCR8 can selectively eliminate Treg within tumors via antibody-dependent cellular cytotoxicity (ADCC) without affecting peripheral blood Treg, thereby preserving systemic immune homeostasis.

● Progress: Multiple CCR8-targeting monoclonal antibodies have entered clinical trials. Combination with PD-1 inhibitors shows potential for overcoming “immunologically cold tumors.”

Strategy 2: Functional Suppression and Depletion

● Targets: Inhibiting key functional molecules of Treg, such as using anti-CTLA-4 antibodies to deplete Treg via ADCC effects; targeting the TGF-β signaling pathway can also weaken their inhibitory function.

● Outlook: Precisely distinguishing Treg subsets (e.g., thymus-derived tTreg vs. peripherally induced pTreg) and developing corresponding targets is key to achieving more precise, lower-toxicity combination therapies.

IV. Reshaping Autoimmune Disease Treatment: From “Immunosuppression” to “Restoring Tolerance”

In autoimmune diseases, Treg dysfunction leads to persistent immune attacks on self-tissues like islets, joints, and kidneys, causing conditions such as type 1 diabetes and rheumatoid arthritis. Current standard treatments (e.g., glucocorticoids, biologics) primarily involve systemic immunosuppression, which increases infection and malignancy risks. Treg therapies aim to achieve disease-specific immune tolerance.

● Strategy: Adoptive Treg Cell Therapy. Autologous Tregs are isolated from the patient, expanded in vitro, and may be genetically engineered to target specific autoantigens (e.g., insulin peptides for type 1 diabetes) before being reinfused into the patient.

● Progress and Outlook:

Type 1 Diabetes: Multiple early-phase clinical trials indicate Treg infusion is safe and shows potential to delay beta cell function decline.

Graft-versus-Host Disease (GvHD): As a complication following stem cell transplantation, Treg infusion has been demonstrated to effectively reduce GvHD severity without compromising anti-leukemic efficacy.

● Future Directions: Developing “antigen-specific Tregs” represents a core challenge. Utilizing CAR-T technology (CAR-Treg) or TCR gene editing techniques can guide Tregs to precisely homing to diseased tissues, achieving localized, efficient, and sustained immunosuppression while avoiding systemic side effects.

V. Future Landscape of Treg Therapy

The Nobel Prize award carries significant weight to the field of Treg therapy. It signifies a shift in our understanding and therapeutic approaches toward the immune system—from a “warfare” model to a “governance” model. Whether stabilizing autoimmune conditions through Treg infusion or unleashing anti-cancer immunity by selectively eliminating tumor-associated Tregs, the core principle remains the precise “retuning” of immune equilibrium. This Nobel Prize-driven wave will profoundly reshape the therapeutic landscape for cancer and autoimmune diseases over the next decade, propelling cell therapy into a new 2.0 era.

VI. Products of Yeasen Biotech Support Treg Function Research

The function of Treg relies on a complex molecular network involving their unique transcription factors, surface receptors, secreted cytokines, and associated signaling proteins. Below is a detailed classification summary of relevant target proteins, cytokines, ELISA kits and antibodies for research.

1. Key Target Proteins and Molecules

These molecules serve as core targets for Treg identification, functional studies, and drug development.

Category	Molecular	Primary Function and Significance
Signature Transcription Factor	Foxp3	The most specific marker for Tregs, acting as the master regulator of Treg development and function. Foxp3 expression and stability directly determine Treg inhibitory function.
Surface Receptors	CD25	Highly expressed on Treg surfaces, serving as an early marker for Treg isolation.
	CTLA-4	Constitutively high-expressed on Treg surfaces.
	GITR	A marker of Treg activation, it modulates Treg inhibitory function.
	ICOS	An inducible co-stimulatory molecule involved in Treg stability and function.
	PD-1	Highly expressed on Tregs in the tumor microenvironment, associated with their immunosuppressive function.
Function-Related Molecules	Helios	A transcription factor often used to distinguish thymus-derived natural Tregs from peripherally induced Tregs.
	CD39/CD73	These molecules synergistically hydrolyze extracellular ATP into adenosine, which exerts immunosuppressive effects.

 2. Key Cytokines

Cytokines	Functions
TGF-β	Key differentiation factor: In vitro and in vivo, it acts synergistically with IL-2 to induce naive T cells into Tregs.
IL-2	Survival factor: Essential for Treg survival, proliferation, and functional maintenance. Tregs “steal” IL-2 via high CD25 expression to suppress Teff growth.
IL-10	Inhibitory cytokine: Secreted by certain Treg subsets (e.g., Tr1 cells) to directly mediate immunosuppression.
IL-35	Inhibitory Cytokine: Primarily secreted by Tregs.

3. ELISA Kits

ELISA kits are used for quantitative detection of soluble protein concentrations in samples such as cell culture supernatants, serum, and plasma.

1) Human Foxp3 ELISA Kit: Detects Foxp3 protein levels in human peripheral blood mononuclear cell lysates or tissue lysates, indirectly reflecting Treg abundance.

2) TGF-β1 ELISA Kit: Detects TGF-β1 concentration in samples.

3) IL-10 ELISA Kit: Detects IL-10 levels secreted by Tregs or other immune cells.

4) IL-2 ELISA Kit: Detects IL-2 levels in the microenvironment to analyze Treg survival status.

5) Soluble CTLA-4 ELISA Kit: Detects soluble CTLA-4 levels in blood, associated with autoimmune diseases and tumor immunity.

4. Antibodies

Antibodies are primarily used in flow cytometry, Western Blot, immunohistochemistry, and other experiments to identify, sort, and visualize Tregs.

1) For Flow Cytometry (Surface and Intracellular Staining):

● Surface Marker Combination (for Sorting/Identification): Anti-CD4, Anti-CD25, Anti-CD127. CD127 is the IL-7 receptor α chain, which is downregulated on Tregs. Thus, CD4⁺ CD25^high CD127^low is the classic strategy for flow cytometric identification and sorting of Tregs.

● Key Transcription Factor/Intracellular Protein Staining:

Anti-Foxp3: Membrane-breaking and fixation are required prior to intracellular staining.

Anti-Helios: Co-stained with Foxp3 to further distinguish Treg subsets.

Other Functional Protein Staining: Anti-CTLA-4, Anti-Ki-67 (proliferation marker), etc.

2) For Functional Studies/Western Blot:

● Anti-Foxp3, Anti-CTLA-4, Anti-Phospho-STAT5 (downstream molecule of IL-2 signaling pathway), etc., for analyzing Treg protein expression and signaling pathways.

Yeasen Biotech's high-quality products are suitable for Treg-related functional studies. We wish you successful experimental outcomes.

Ordering information

Product Category	Product Name	Item No.
Target Proteins	Recombinant Human HLA-A*02:01&B2M&Foxp3 (TLIRWAILEA) Monomer Protein, His-Avi Tag	96004ES
	Recombinant Human IL-2 R alpha/CD25 Protein, His-Avi Tag	93903ES
	Recombinant Mouse IL-2 R alpha/CD25 Protein, His Tag	95609ES
	Recombinant Human CTLA-4/CD152 (C-His Tag)	93553ES
	Recombinant Mouse CTLA4 Protein, His Tag	93451ES
	Recombinant Human GITR/TNFRSF18 (His Tag)	93554ES
	Recombinant Mouse GITR/TNFRSF18 Protein, His Tag	93690ES
	Recombinant Human ICOS/CD278 (His Tag)	94127ES
	Recombinant Mouse ICOS/CD278 Protein, hFc Tag	94795ES
	Recombinant Human PD-1/PDCD1 Protein, His Tag	93558ES
	Recombinant Mouse PD-1/PDCD1 Protein, hFc Tag	93670ES
Cytokines	Recombinant Human IL-10 Protein	90109ES
	Recombinant Mouse IL-10 Protein	90149ES
	Recombinant Human/Mouse/Rat TGF-beta 1/TGF-β1 Protein	91701ES
	Recombinant Human TGF-β2 Protein (CHO)	91709ES
	Recombinant Human TGF-beta 3 Protein	91705ES
	Recombinant Human IL-2 Protein (CHO)	90267ES
	Recombinant Mouse IL-2 Protein	90142ES
ELISA Kits	Human IL-10 ELISA Kit	97063ES
	Mouse IL-10 ELISA Kit	98025ES
	Human IL-2 ELISA Kit	97029ES
Antibodies	FOXP3 Mouse mAb	31061ES
	Anti-IL-2Ra / CD25 Reference Antibody (daclizumab)	31765ES
	Human CTLA4 Detection Antibody	37116ES
	CD4 Rabbit mAb	772985ES
	Purified Mouse Anti-Human CD4 mAb	32111ES
	CD127 Rabbit mAb	767495ES
	CD127 Mouse mAb	769851ES
	Ki67 Rabbit mAb	772939ES
	Ki67 Rat mAb	773072ES

1. Image source：www.nobelprize.org

2. Ghobadinezhad F, Ebrahimi N, Mozaffari F, Moradi N, Beiranvand S, Pournazari M, et al. The emerging role of regulatory cell-based therapy in autoimmune disease. Frontiers in Immunology 2022; 13.