TY - JOUR
T1 - Spatial immunophenotypes predict response to anti-PD1 treatment and capture distinct paths of T cell evasion in triple negative breast cancer
AU - Hammerl, Dora
AU - Martens, John W. M.
AU - Timmermans, Mieke
AU - Smid, Marcel
AU - Trapman-Jansen, Anita M.
AU - Foekens, Renée
AU - Isaeva, Olga I.
AU - Voorwerk, Leonie
AU - Balcioglu, Hayri E.
AU - Wijers, Rebecca
AU - Nederlof, Iris
AU - Salgado, Roberto
AU - Horlings, Hugo
AU - Kok, Marleen
AU - Debets, Reno
N1 - Funding Information: Authors thank Carolien van Deurzen and Maxine Cooks for providing FFPE tissue of TNBC LN metastases as well as the Dutch Cancer Society (KWF project number 2014-7087) for financial support. Publisher Copyright: © 2021, The Author(s).
PY - 2021/12/1
Y1 - 2021/12/1
N2 - Only a subgroup of triple-negative breast cancer (TNBC) responds to immune checkpoint inhibitors (ICI). To better understand lack of response to ICI, we analyze 681 TNBCs for spatial immune cell contextures in relation to clinical outcomes and pathways of T cell evasion. Excluded, ignored and inflamed phenotypes can be captured by a gene classifier that predicts prognosis of various cancers as well as anti-PD1 response of metastatic TNBC patients in a phase II trial. The excluded phenotype, which is associated with resistance to anti-PD1, demonstrates deposits of collagen-10, enhanced glycolysis, and activation of TGFβ/VEGF pathways; the ignored phenotype, also associated with resistance to anti-PD1, shows either high density of CD163+ myeloid cells or activation of WNT/PPARγ pathways; whereas the inflamed phenotype, which is associated with response to anti-PD1, revealed necrosis, high density of CLEC9A+ dendritic cells, high TCR clonality independent of neo-antigens, and enhanced expression of T cell co-inhibitory receptors.
AB - Only a subgroup of triple-negative breast cancer (TNBC) responds to immune checkpoint inhibitors (ICI). To better understand lack of response to ICI, we analyze 681 TNBCs for spatial immune cell contextures in relation to clinical outcomes and pathways of T cell evasion. Excluded, ignored and inflamed phenotypes can be captured by a gene classifier that predicts prognosis of various cancers as well as anti-PD1 response of metastatic TNBC patients in a phase II trial. The excluded phenotype, which is associated with resistance to anti-PD1, demonstrates deposits of collagen-10, enhanced glycolysis, and activation of TGFβ/VEGF pathways; the ignored phenotype, also associated with resistance to anti-PD1, shows either high density of CD163+ myeloid cells or activation of WNT/PPARγ pathways; whereas the inflamed phenotype, which is associated with response to anti-PD1, revealed necrosis, high density of CLEC9A+ dendritic cells, high TCR clonality independent of neo-antigens, and enhanced expression of T cell co-inhibitory receptors.
UR - http://www.scopus.com/inward/record.url?scp=85115813215&partnerID=8YFLogxK
U2 - https://doi.org/10.1038/s41467-021-25962-0
DO - https://doi.org/10.1038/s41467-021-25962-0
M3 - Article
C2 - 34580291
SN - 2041-1723
VL - 12
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 5668
ER -