Quantitatively defined stromal B cell aggregates are associated with response to checkpoint inhibitors in unresectable melanoma Journal Article


Authors: Smithy, J. W.; Peng, X.; Ehrich, F. D.; Moy, A. P.; Yosofvand, M.; Maher, C.; Aleynick, N.; Vanguri, R.; Zhuang, M.; Lee, J.; Bleile, M.; Li, Y.; Postow, M. A.; Panageas, K. S.; Hollmann, T. J.; Callahan, M. K.; Shen, R.
Article Title: Quantitatively defined stromal B cell aggregates are associated with response to checkpoint inhibitors in unresectable melanoma
Abstract: Multiplex immunofluorescence (mIF) is a promising tool for immunotherapy biomarker discovery in melanoma and other solid tumors. mIF captures detailed phenotypic information of immune cells in the tumor microenvironment, as well as spatial data that can reveal biologically relevant interactions among cell types. Given the complexity of mIF data, the development of automated analysis pipelines is crucial for advancing biomarker discovery. In pre-treatment melanoma samples from 50 patients treated with immune checkpoint inhibitors (ICIs), a higher stromal B cell percentage is associated with the clinical benefit of ICI therapy. The automatic detection of B cell aggregates with DBSCAN, a novel application of a computer-aided machine learning algorithm, demonstrates the potential for enhanced accuracy compared to pathologist assessment of lymphoid aggregates. TCF1+ and LAG3− T cell subpopulations are enriched near stromal B cells, suggesting potential functional interactions. These analyses provide a roadmap for the further development of spatial immunotherapy biomarkers in melanoma and other diseases. © 2025 The Author(s)
Keywords: melanoma; spatial analysis; immune checkpoint inhibitors; tertiary lymphoid structures; multiplex immunofluorescence; cp: cancer
Journal Title: Cell Reports
Volume: 44
Issue: 4
ISSN: 2211-1247
Publisher: Cell Press  
Date Published: 2025-04-22
Start Page: 115554
Language: English
DOI: 10.1016/j.celrep.2025.115554
PROVIDER: scopus
PUBMED: 40220297
DOI/URL:
Notes: Article -- MSK Cancer Center Support Grant (P30 CA008748) acknowledged in PDF -- MSK corresponding author is James Smithy -- Source: Scopus
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MSK Authors
  1. Michael Andrew Postow
    361 Postow
  2. Katherine S Panageas
    512 Panageas
  3. Colleen Anne Maher
    16 Maher
  4. Andrea Primiani Moy
    32 Moy
  5. James William Smithy
    28 Smithy
  6. Jasme Lee
    31 Lee
  7. Roger Shen
    4 Shen
  8. Fiona Donovan Ehrich
    10 Ehrich
  9. Mingqiang Zhuang
    3 Zhuang
  10. Mary Lena Bleile
    1 Bleile