Quantitative, architectural analysis of immune cell subsets in tumor-draining lymph nodes from breast cancer patients and healthy lymph nodes.
BACKGROUND
To date, pathological examination of specimens remains largely qualitative. Quantitative measures of tissue spatial features are generally not captured. To gain additional mechanistic and prognostic insights, a need for quantitative architectural analysis arises in studying immune cell-cancer interactions within the tumor microenvironment and tumor-draining lymph nodes (TDLNs).


RESULTS
We present a novel, quantitative image analysis approach incorporating 1) multi-color tissue staining, 2) high-resolution, automated whole-section imaging, 3) custom image analysis software that identifies cell types and locations, and 4) spatial statistical analysis. As a proof of concept, we applied this approach to study the architectural patterns of T and B cells within tumor-draining lymph nodes from breast cancer patients versus healthy lymph nodes. We found that the spatial grouping patterns of T and B cells differed between healthy and breast cancer lymph nodes, and this could be attributed to the lack of B cell localization in the extrafollicular region of the TDLNs.


CONCLUSIONS
Our integrative approach has made quantitative analysis of complex visual data possible. Our results highlight spatial alterations of immune cells within lymph nodes from breast cancer patients as an independent variable from numerical changes. This opens up new areas of investigations in research and medicine. Future application of this approach will lead to a better understanding of immune changes in the tumor microenvironment and TDLNs, and how they affect clinical outcomes.
Setiadi
A Francesca
AF
Department of Medicine, Stanford University School of Medicine, Stanford, California, United States of America.
Ray
Nelson C
NC
Kohrt
Holbrook E
HE
Kapelner
Adam
A
Carcamo-Cavazos
Valeria
V
Levic
Edina B
EB
Yadegarynia
Sina
S
van der Loos
Chris M
CM
Schwartz
Erich J
EJ
Holmes
Susan
S
Lee
Peter P
PP
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016175:B-Lymphocyte Subsets / Q000378:metabolism*; D001943:Breast Neoplasms / Q000175:diagnosis / Q000276:immunology* / Q000473:pathology*; D016022:Case-Control Studies; D002452:Cell Count; D006801:Humans; D008198:Lymph Nodes / Q000276:immunology*; D008207:Lymphatic Metastasis; D008875:Middle Aged; D057054:Molecular Imaging / Q000379:methods*; D011379:Prognosis; D016176:T-Lymphocyte Subsets / Q000378:metabolism*
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