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Purpose <p>Medulloblastomas are aggressive pediatric brain tumors. Whereas Wnt-driven tumors are associated with a favorable prognosis, other molecular variants have poorer survival. This study uses a transcriptomic algorithm to assess T-cell dysfunction and exclusion signatures that may predict response to immunotherapy.</p> Methods <p>The Gene Expression Omnibus (GEO) was queried for bulk RNA-seq data for medulloblastomas. Samples were extracted as transcripts per million (TPM)–normalized matrices and corrected for batch effects. The TIDE model was used to calculate tumor immune dysfunction and exclusion scores for each sample. Cytotoxic T-cell levels were assessed to classify tumors as immunologically cold or hot. The algorithm identifies tumors that are either (1) cold with no T-cell exclusion or (2) hot with no T-cell dysfunction as potential responders to immune checkpoint blockade (ICB).</p> Results <p>262 pediatric samples were identified. The average TIDE score was + 0.05 (SD: 0.76), with 134 (51.1%) predicted ICB responders. Although 237 tumors were CTL-low, 127 (53.6%) of these were still predicted responders. By molecular subgroup, 70 samples were Group 3, 89 Group 4, 71 Shh-driven, and 32 Wnt-driven. Subgroup predicted ICB response (<i>p</i> &lt; 0.001), with more responders in Group 3 (mean TIDE: −0.43, SD: 0.62) and Group 4 (mean TIDE: −0.17, SD: 0.59).</p> Conclusion <p>This transcriptomic analysis suggests that specific molecular subgroups of medulloblastoma harbor immunologic features associated with potential responsiveness to ICB therapy.</p>

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Profiling T-cell activity and exclusion in pediatric medulloblastoma highlights immunotherapy-responsive subgroups

  • 期刊论文

  • 发表日期：

    2026年1月21日

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  • Shaan Bhandarkar,
  • Matteo Palermo,
  • Charles Wu,
  • Saket Myneni,
  • Saahith Potluri,
  • Arjit Singh,
  • Connor Liu,
  • A. Karim Ahmed,
  • Debraj Mukherjee

摘要

Purpose

Medulloblastomas are aggressive pediatric brain tumors. Whereas Wnt-driven tumors are associated with a favorable prognosis, other molecular variants have poorer survival. This study uses a transcriptomic algorithm to assess T-cell dysfunction and exclusion signatures that may predict response to immunotherapy.

Methods

The Gene Expression Omnibus (GEO) was queried for bulk RNA-seq data for medulloblastomas. Samples were extracted as transcripts per million (TPM)–normalized matrices and corrected for batch effects. The TIDE model was used to calculate tumor immune dysfunction and exclusion scores for each sample. Cytotoxic T-cell levels were assessed to classify tumors as immunologically cold or hot. The algorithm identifies tumors that are either (1) cold with no T-cell exclusion or (2) hot with no T-cell dysfunction as potential responders to immune checkpoint blockade (ICB).

Results

262 pediatric samples were identified. The average TIDE score was + 0.05 (SD: 0.76), with 134 (51.1%) predicted ICB responders. Although 237 tumors were CTL-low, 127 (53.6%) of these were still predicted responders. By molecular subgroup, 70 samples were Group 3, 89 Group 4, 71 Shh-driven, and 32 Wnt-driven. Subgroup predicted ICB response (p < 0.001), with more responders in Group 3 (mean TIDE: −0.43, SD: 0.62) and Group 4 (mean TIDE: −0.17, SD: 0.59).

Conclusion

This transcriptomic analysis suggests that specific molecular subgroups of medulloblastoma harbor immunologic features associated with potential responsiveness to ICB therapy.