Cancer Biology

Depletion of rRNA Methyltranferase METTL5 Enhances Anti-Tumor Immune Response via Neoantigen Generated from Cryptic Translation

1. Yangyi Zhang
2. Xiaoyan Shi
3. Yuci Wang
4. Ruiqi Wang
5. Folan Lin
6. Yanlan Cao
7. Wanqiu Li
8. Hao Chen

• Curated by eLife

  eLife Assessment

  This study presents a valuable finding that depletion of the rRNA methyltransferase METTL5 enhances anti-tumor immunity through a novel mechanism involving neoantigen generation from non-canonical translation. The evidence supporting the central conclusions is solid, with comprehensive multi-omics data including ribosome profiling, immunopeptidomics, TCR sequencing, and multiple in vivo tumor models demonstrating synergy with immune checkpoint blockade.

Reviewed by eLife

Myosin VI orchestrates estrogen-driven gene expression in breast cancer cells

1. Yukti Hari-Gupta
2. Danielle Lambert
3. Isabel W. Shahid-Fuente
4. Natalia Fili
5. Ália dos Santos
6. Alexandria Sprules
7. Hyejeong Rosemary Kim
8. Alexander W. Cook
9. Peter J.I. Ellis
10. Jesse Aaron
11. Teng-Leong Chew
12. Lin Wang
13. Christopher P. Toseland

Reviewed by PREreview

Identifying tissue states by spatial protein patterns related to chemotherapy response in triple-negative breast cancer

1. Luciana M Luque
2. Mohammad Asif Khan
3. Giuseppe Torrisi
4. Tessa D Green
5. David Hardman
6. Claudia Owczarek
7. Tom A Phillips
8. Debora S Marks
9. Maddy Parsons
10. Chris Sander
11. Linus J Schumacher

• Curated by eLife

  eLife Assessment

  This is an important work implementing data mining methods on IMC data to discover spatial protein patterns related to the triple-negative breast cancer patients' chemotherapy response. The evidence supporting the claims of the authors is solid, although more detailed methodology clarification and validation are needed. While the accuracy of the methods is not very high, the work shows potential for translational application.

Reviewed by eLife

Punctuated mutagenesis promotes multi-step evolutionary adaptation in human cancers

1. Christopher Graser
2. Wenbo Wu
3. Cole Christini
4. Mia Petljak
5. Franziska Michor

• Curated by eLife

  eLife Assessment

  This valuable study presents a theoretical model of how punctuated mutations influence multistep adaptation, supported by empirical evidence from some TCGA cancer cohorts. This solid model points to the case of possible punctuated evolution rather than gradual genomic change. There was some disagreement amongst the reviewers in terms of how closely the theoretical results apply to the phenomena examined empirically, and alternative explanations should be considered in the future.

Reviewed by eLife

CNN-based learning of single-cell transcriptomes reveals a blood-detectable multi-cancer signature of brain metastasis

1. Ryan Lusby
2. Debojyoti Chowdhury
3. Sarah Carl
4. Vijay K Tiwari

• Curated by eLife

  eLife Assessment

  This important study describes a deep learning framework that analyzes single-cell RNA data to identify a tumor-agnostic gene signature associated with brain metastases. The identified signature uncovers key molecular mechanisms, highlights potential therapeutic targets, and demonstrates a metastasis-specific transcriptional signal in circulating platelets, suggesting its promise for non-invasive diagnostics through liquid biopsy. The evidence supporting the findings is solid, utilizing interpretable deep learning methodologies and large-scale datasets across multiple cancer types, though some aspects may benefit from additional analysis and validation.

Reviewed by eLife

Androgen deprivation triggers a cytokine signaling switch to induce immune suppression and prostate cancer recurrence

1. Kai Sha
2. Renyuan Zhang
3. Aerken Maolake
4. Shalini Singh
5. Gurkamal Chatta
6. Kevin H Eng
7. Kent L Nastiuk
8. John J Krolewski

• Curated by eLife

  eLife Assessment

  This potentially valuable work aimed at a better understanding of the mechanisms of response and resistance to androgen deprivation therapy in prostate cancer using genetically engineered mouse models. A key observation relates to the timing of TNF blockage therapy and the concept of a "TNF switch." The solid data were collected using conventional approaches and the conclusions are mostly justified, particularly with the inclusion of more detailed statistics in the revision. The work will be of interest to the prostate cancer research community.

Reviewed by eLife