Thymosin alpha-1 · research summary

Thymosin α1 reverses oncolytic adenovirus-induced M2 polarization of macrophages to improve antitumor immunity and therapeutic efficacy.

Cell reports. Medicine · 2024. Summary drawn from the study's full text. Each statement is followed by the exact sentence it comes from. This is a research summary, not medical advice.

Study type

Preclinical study using in vitro cell cultures and in vivo murine tumor models
“we confirm this hypothesis in a variety of solid tumor models and in vitro cell experiments.”

Subjects

Murine tumor models (4T1, CT26, H22), humanized mouse models, and cell lines (RAW264.7, THP-1, 4T1, MDA-MB-231)
“we confirm this hypothesis in a variety of solid tumor models and in vitro cell experiments.”

Sample size

Varied by experiment, ranging from 3 to 10 biological replicates per group
“n = 6 biological replicates”

Duration

Experiments monitored tumor growth and immune infiltration over periods up to 90 days post-treatment initiation
“The cured mice with immunological memory were again rechallenged with 5 × 106 H22 cells and the opposing flank was injected subcutaneously with 5×105 4T1 cells on day 90 after the first rechallenge”

Reported findings

Type V adenovirus induces M2 polarization of tumor-associated macrophages and increases regulatory T cell infiltration
“Here, we demonstrate that type V adenovirus (ADV) induces the polarization of tumor-associated macrophages (TAMs) to the M2 phenotype and increases the infiltration of regulatory T cells (Tregs) in the tumor microenvironment (TME).”
Thymosin alpha 1 reprograms M2-like macrophages toward an antitumoral phenotype and reduces Treg infiltration
“By selectively compensating for these deficiencies, thymosin alpha 1 (Tα1) reprograms “M2-like” TAMs toward an antitumoral phenotype, thereby reprogramming the TME into a state more beneficial for antitumor immunity.”
Recombinant adenovirus expressing Tα1 (ADVTα1) enhances antitumor efficacy via CD8+ T cells
“Both exogenously supplied and adenovirus-produced Tα1 orchestrate TAM reprogramming and enhance the antitumor efficacy of ADV via CD8+ T cells, showing promising prospects for clinical translation.”

Limitations stated by the authors

Lack of patient samples from clinical trials, undefined changes in macrophage antigen-presenting function, and incomplete understanding of precise molecular mechanisms
“No patient samples have been obtained from existing oncolytic adenovirus clinical trials to demonstrate an immune feedback loop mediated by OV treatment, which is critical for clinical translational prospects.”

Source: PubMed 39357524 · DOI 10.1016/j.xcrm.2024.101751 · all study summaries

Duration

Experiments monitored tumor growth and immune infiltration over periods up to 90 days post-treatment initiation

“The cured mice with immunological memory were again rechallenged with 5 × 106 H22 cells and the opposing flank was injected subcutaneously with 5×105 4T1 cells on day 90 after the first rechallenge”

Reported findings

Type V adenovirus induces M2 polarization of tumor-associated macrophages and increases regulatory T cell infiltration

“Here, we demonstrate that type V adenovirus (ADV) induces the polarization of tumor-associated macrophages (TAMs) to the M2 phenotype and increases the infiltration of regulatory T cells (Tregs) in the tumor microenvironment (TME).”

Thymosin alpha 1 reprograms M2-like macrophages toward an antitumoral phenotype and reduces Treg infiltration

“By selectively compensating for these deficiencies, thymosin alpha 1 (Tα1) reprograms “M2-like” TAMs toward an antitumoral phenotype, thereby reprogramming the TME into a state more beneficial for antitumor immunity.”

Recombinant adenovirus expressing Tα1 (ADVTα1) enhances antitumor efficacy via CD8+ T cells

“Both exogenously supplied and adenovirus-produced Tα1 orchestrate TAM reprogramming and enhance the antitumor efficacy of ADV via CD8+ T cells, showing promising prospects for clinical translation.”

Limitations stated by the authors

Lack of patient samples from clinical trials, undefined changes in macrophage antigen-presenting function, and incomplete understanding of precise molecular mechanisms

“No patient samples have been obtained from existing oncolytic adenovirus clinical trials to demonstrate an immune feedback loop mediated by OV treatment, which is critical for clinical translational prospects.”