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@alicefrolov.bsky.socialSep 12, 2026, 5:18 PM

Sharing a new data visualization exploring the phenotypic reprogramming of exhausted CD8+ T cells following PD-1 axis blockade.

#TcellExhaustion #CheckpointBlockade #TumorImmunology #CD8Tcells #AntiPD1 #Tpex #ImmuneCheckpoint #CancerImmunotherapy

Sharing a new data visualization exploring the phenotypic reprogramming of exhausted CD8+ T cells following PD-1 axis blockade.

Figure: "Reprogramming exhausted CD8+ T cells with anti-PD-1 therapy"
Subtitle: "Marker-defined transitions from terminal exhaustion toward progenitor/effector states after checkpoint blockade"

The visualization employs a faceted marginal-distribution slope arrow design, functioning as a state-transition flow map. Each facet corresponds to a defined exhaustion-associated marker axis (TCF1, TOX, TIM-3, PD-1, GZMB, and Ki-67), with paired marginal distributions rendered pre- and post-treatment. Slope arrows connect the density centroids across conditions, encoding both the directionality and relative magnitude of population-level marker shifts. This approach was chosen to make explicit the differential mobilization of progenitor-exhausted (Tpex) versus terminally exhausted (Tex_term) subsets rather than collapsing the transition into a single trajectory summary.

The simulated data are calibrated to reproduce trends consistent with the current literature. Under anti-PD-1, the TCF1+ TOX-intermediate progenitor compartment shows expansion accompanied by upward slope vectors in Ki-67 and GZMB, consistent with proliferative burst and reacquisition of effector potential. Concurrently, the TIM-3-high, TCF1-negative terminally differentiated fraction contracts, and its centroid displays limited displacement along the TCF1 axis, reflecting the constrained plasticity of terminally exhausted cells. This asymmetry underscores that checkpoint blockade preferentially acts on the Tpex reservoir rather than fully reverting terminal exhaustion, a distinction with direct implications for durability of response.
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