Command Palette

Search for a command to run...

Preprint WatchMildJune 11th, 2026

Profilin-1 Deficiency Activates STING to Drive T Cell-Mediated Anti-Tumor Immunity in Breast Cancer

Eder, I.; Baghaei, M.; Maurya, S.; Yu, V.; Wilson, E.; Kashkoush, A.; Liu, J.-J.; Liu, S.; Luo, J.; Storkus, W.; Roy, P.

Profilin-1 loss in breast cancer cells activates the cGAS-STING pathway and a type I interferon response that drives CD8 T-cell-mediated tumor regression.

Mild contradiction

1 prior failure

One documented clinical failure (Phase 1 or 2) overlaps with the claimed mechanism.

This preprint reinforces the mechanism behind the single indexed STING1 failure rather than contradicting it. The IMSA101 program (imsa101-sting-agonist-immunesensor-shutdown) ended on a sponsor decision, not on a biological or efficacy result, so the target's anti-tumor rationale was never tested to failure in that trial. Eder and colleagues show that Profilin-1 loss in breast cancer cells generates cytosolic DNA, activates cGAS-STING and type I interferon signaling, and drives CD8 T-cell-dependent tumor regression in an immunocompetent model. That result supports STING activation as a route to anti-tumor immunity and points to commercial context rather than mechanism as the reason the indexed program stopped. The flag is mild because the documented failure was operational and the preprint aligns with, rather than challenges, the target rationale.

Abstract excerpt

Dysregulation of actin-binding protein Profilin1 (Pfn1) in tumor cells has prominent impacts on tumor progression. Using an inducible CRISPR/Cas9 knockout model, Pfn1 depletion in breast cancer cells produced genomic instability, nuclear envelope abnormality, and cytosolic DNA accumulation, which activated the cGAS-STING pathway and a type I interferon response including STING-mediated upregulation of pro-inflammatory chemokines. In an immunocompetent mouse model, tumor-cell Pfn1 loss promoted an immunogenic microenvironment with increased intratumoral CD8 T cells and robust tumor regression that required an intact immune system and was reversed by CD8 T-cell depletion.

Matching Claidex post-mortems

1 of 1 indexed

This is an automated contradiction flag, not an editorial judgment on the preprint's quality. Flags identify where the preclinical literature and the clinical failure record diverge.