Open AccessSpatial clustering of CD68+ tumor associated macrophages with tumor cells is associated with worse overall survival in metastatic clear cell renal cell carcinoma
Author(s) -
Nicholas H. Chakiryan,
Gregory J. Kimmel,
YoungChul Kim,
Ali Hajiran,
Ahmet Aydın,
Logan Zemp,
Esther N. Katende,
Jonathan V. Nguyen,
Neale Lopez-Blanco,
Jad Chahoud,
Philippe E. Spiess,
Michelle Fournier,
Jasreman Dhillon,
Liang Wang,
Carlos MoranSegura,
Asmaa El-Kenawi,
James J. Mulé,
Philipp M. Altrock,
Brandon Manley
Publication year - 2021
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0245415
Subject(s) - cd68 , stromal cell , immune system , cancer research , clear cell renal cell carcinoma , biology , tumor microenvironment , cell , pathology , tumor associated macrophage , immunohistochemistry , renal cell carcinoma , medicine , immunology , genetics
Immune infiltration is typically quantified using cellular density, not accounting for cellular clustering. Tumor-associated macrophages (TAM) activate oncogenic signaling through paracrine interactions with tumor cells, which may be better reflected by local cellular clustering than global density metrics. Using multiplex immunohistochemistry and digital pathologic analysis we quantified cellular density and cellular clustering for myeloid cell markers in 129 regions of interest from 55 samples from 35 patients with metastatic ccRCC. CD68+ cells were found to be clustered with tumor cells and dispersed from stromal cells, while CD163+ and CD206+ cells were found to be clustered with stromal cells and dispersed from tumor cells. CD68+ density was not associated with OS, while high tumor/CD68+ cell clustering was associated with significantly worse OS. These novel findings would not have been identified if immune infiltrate was assessed using cellular density alone, highlighting the importance of including spatial analysis in studies of immune cell infiltration of tumors. Significance : Increased clustering of CD68+ TAMs and tumor cells was associated with worse overall survival for patients with metastatic ccRCC. This effect would not have been identified if immune infiltrate was assessed using cell density alone, highlighting the importance of including spatial analysis in studies of immune cell infiltration of tumors.