Thymosin α1 protects from CTLA-4 intestinal immunopathology.

Renga G, Bellet MM, Pariano M, Gargaro M, Stincardini C, D'Onofrio F, Mosci P, Brancorsini S, Bartoli A, Goldstein AL, Garaci E, Romani L, Costantini C

Life science alliance14 Aug 2020Cited by 26 (Europe PMC)

PMID32817121PMCIDPMC7441522DOI10.26508/lsa.202000662PepBankPUB-32817121

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Summary

The advent of immune checkpoint inhibitors has represented a major boost in cancer therapy, but safety concerns are increasingly being recognized. Indeed, although beneficial at the tumor site, unlocking a safeguard mechanism of the immune response may trigger autoimmune-like effects at the periphery, thus making the safety of immune checkpoint inhibitors a research priority. Herein, we demonstrate that thymosin α1 (Tα1), an endogenous peptide with immunomodulatory activities, can protect mice from intestinal toxicity in a murine model of immune checkpoint inhibitor-induced colitis. Specifically, Tα1 efficiently prevented immune adverse pathology in the gut by promoting the indoleamine 2,3-dioxygenase (IDO) 1-dependent tolerogenic immune pathway. Notably, Tα1 did not induce IDO1 in the tumor microenvironment, but rather modulated the infiltration of T-cell subsets by inverting the ratio between CD8⁺ and Treg cells, an effect that may depend on Tα1 ability to regulate the differentiation and chemokine expression profile of DCs. Thus, through distinct mechanisms that are contingent upon the context, Tα1 represents a plausible candidate to improve the safety/efficacy profile of immune checkpoint inhibitors.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study4

4 results from studies that gave the peptide. No result from this study comes from people.

01AnimalAnimal study (in vivo)Efficacy outcome
In mice with immune checkpoint inhibitor-induced colitis, thymosin α1 protected against intestinal toxicity and immune adverse pathology in the gut.
In plain wordsIn mice, thymosin α1 protected the gut from damage caused by a checkpoint inhibitor.
Peptide
Thymosin alpha-1
Outcome
DecreaseIntestinal toxicity in checkpoint inhibitor-induced colitis
Study
mousen: not reported in source
Immune checkpoint inhibitor-induced colitis
Outcome group
Gastrointestinal protection · Gastrointestinal
Studied dose
Dose not stated
Source sentences
Summary
Herein, we demonstrate that thymosin α1 (Tα1), an endogenous peptide with immunomodulatory activities, can protect mice from intestinal toxicity in a murine model of immune checkpoint inhibitor-induced colitis.
1 context sentence(design, population, supporting numbers)
Summary · context
Tα1 efficiently prevented immune adverse pathology in the gut
Show in the study text Report a problemFND-3281712101
02AnimalAnimal study (in vivo)Mechanism
In mice with checkpoint inhibitor-induced colitis, thymosin α1 promoted the IDO1-dependent tolerogenic immune pathway.
In plain wordsIn mice, thymosin α1 boosted an immune pathway that calms the gut immune response.
Peptide
Thymosin alpha-1
Outcome
IncreaseIDO1-dependent tolerogenic immune pathway in the gut
Study
mousen: not reported in source
Immune checkpoint inhibitor-induced colitis
Outcome group
Immune response · Immune and inflammation
Studied dose
Dose not stated
Source sentences
Summary
by promoting the indoleamine 2,3-dioxygenase (IDO) 1-dependent tolerogenic immune pathway.
Show in the study text Report a problemFND-3281712102
03AnimalAnimal study (in vivo)Mechanism
In mice with checkpoint inhibitor-induced colitis and tumors, thymosin α1 did not induce IDO1 in the tumor microenvironment.
In plain wordsIn mice, thymosin α1 did not raise IDO1 inside the tumor.
Peptide
Thymosin alpha-1
Outcome
No significant changeIDO1 induction in the tumor microenvironment
Study
mousen: not reported in source
Immune checkpoint inhibitor-induced colitis
Outcome group
Immune response · Cancer
Studied dose
Dose not stated
Source sentences
Summary
Tα1 did not induce IDO1 in the tumor microenvironment
Show in the study text Report a problemFND-3281712103
04AnimalAnimal study (in vivo)Mechanism
In mice with tumors, thymosin α1 modulated the infiltration of T-cell subsets by inverting the ratio between CD8+ and Treg cells.
In plain wordsIn mice, thymosin α1 changed the balance of T-cell types that enter the tumor.
Peptide
Thymosin alpha-1
Outcome
MixedCD8+ to Treg cell ratio in the tumor microenvironment
Study
mousen: not reported in source
Immune checkpoint inhibitor-induced colitis
Outcome group
Immune response · Cancer
Studied dose
Dose not stated
Source sentences
Summary
modulated the infiltration of T-cell subsets by inverting the ratio between CD8⁺ and Treg cells
Show in the study text Report a problemFND-3281712104

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Registered trials2

Trials this study reports on, or that list this study as a reference. Registry data from ClinicalTrials.gov.

2 trials · 1 ongoing · source ClinicalTrials.gov (opens in a new tab)

Active, not recruitingPhase 2NCT06056804

Neoadjuvant Chemoradiotherapy Combined With PD-1 Inhibitor and Thymalfasin for pMMR/MSS Locally Advanced Mid-low Rectal Cancer

Beijing Friendship Hospitaln = 203 Jan 2024 to est. 1 Jul 2027

Locally Advanced Rectal Cancer

Trial page ClinicalTrials.govUpdated 2 Apr 2025

Status unknownPhase 4NCT06178146

Thymosin Alpha-1 for irAE Secondary to ICIs

Jun Wangn = 401 Sept 2023 to est. Apr 2025

IrAE

Trial page ClinicalTrials.govUpdated 20 Dec 2023

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 3Current
10 Oct 2026, 08:55 UTC
Study results updated
Version 2
9 Oct 2026, 03:03 UTC
Study data updated · source update from Europe PMC
Version 1
9 Oct 2026, 03:02 UTC
First added · source update from Europe PMC