cervical-cancer

PIK3CA mutation creates a pro-immune but exhausted tumor microenvironment in cervical cancer—combination therapy may help.

Single-cell transcriptomic atlas of cervical cancer with PIK3CA mutations found a paradoxical TME: T-cell inflammation coexists with resistance to adaptive immune responses. PIK3CA-mutant epithelial cells induce CD8+ T cell exhaustion via both canonical PD-L1-PD-1 and non-canonical SPP1-CD44 signaling. PIK3CA mutations also enrich MMP9+ macrophages promoting angiogenesis via ANGPTL4 signaling. Results provide rational basis for combining PD-1 blockade with anti-angiogenic therapies.

Key Findings

PIK3CA mutations induce T-cell inflammation AND immune resistance simultaneously
PIK3CA mutant cells induce CD8+ T cell exhaustion via PD-L1-PD-1 and SPP1-CD44
PIK3CA mutations enrich MMP9+ macrophages promoting angiogenesis (ANGPTL4 signaling)
PIK3CA mutation is a key predictive biomarker for combination immunotherapy
Rational basis identified for combining PD-1 blockade with anti-angiogenic therapies

Implications

PIK3CA mutation status should guide combination immunotherapy selection in cervical cancer. PD-1 + anti-angiogenic combinations have biological rationale in PIK3CA-mutant CC.

Caveats

Single-cell analysis; abstract-only. Small patient numbers. Functional validation of therapeutic combinations in clinical settings needed.

Source: Frontiers in immunology — 2026-01-01

Landmark DCIS trial, CRC microbiome & AML combos

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GBM Tumor Microenvironment Drug Target Atlas

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BET Inhibitor Target Selectivity Database

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