CD11c-CD8 Spatial Cross Presentation: A Novel Approach to Link Immune Surveillance and Patient Survival in Soft Tissue Sarcoma

CD11c-CD8 Spatial Cross Presentation: A Novel Approach to Link Immune Surveillance and Patient Survival in Soft Tissue Sarcoma

Checkpoint inhibitors are slowly being introduced in the care of specific sarcoma subtypes such as undifferentiated pleomorphic sarcoma, alveolar soft part sarcoma, and angiosarcoma even though formal indication is lacking. Proper biomarkers to unravel potential immune reactivity in the tumor microe...

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Bibliographic Details
Published in:Cancers Vol. 13; no. 5; p. 1175
Main Authors: Su, Yanhong, Tsagkozis, Panagiotis, Papakonstantinou, Andri, Tobin, Nicholas P, Gultekin, Okan, Malmerfelt, Anna, Ingelshed, Katrine, Neo, Shi Yong, Lundquist, Johanna, Chaabane, Wiem, Nisancioglu, Maya H, Leiss, Lina W, Östman, Arne, Bergh, Jonas, Sedimbi, Saikiran, Lehti, Kaisa, Lundqvist, Andreas, Stragliotto, Christina L, Haglund, Felix, Ehnman, Monika
Format: Journal Article
Language:English
Published: Switzerland MDPI AG 09-03-2021
MDPI
Subjects:
Alveoli
Antigen presentation
Antigen-presenting cells
Biomarkers
Cancer therapies
CD11c antigen
CD8 antigen
Chemotherapy
Dendritic cells
Flow cytometry
Foxp3 protein
Gene expression
Immune checkpoint
Immunohistochemistry
Immunosurveillance
Immunotherapy
Kinases
Liposarcoma
Lymphocytes
Medical prognosis
Medicin och hälsovetenskap
Metastasis
Patients
PD-1 protein
PD-L1 protein
Radiation therapy
Sarcoma
Soft tissue sarcoma
Tumor microenvironment
Tumors
antigen-presenting cells
CD8
cross presentation
UPS
immune cells
tumor microenvironment
soft tissue sarcoma
CD11c
liposarcoma
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Summary:Checkpoint inhibitors are slowly being introduced in the care of specific sarcoma subtypes such as undifferentiated pleomorphic sarcoma, alveolar soft part sarcoma, and angiosarcoma even though formal indication is lacking. Proper biomarkers to unravel potential immune reactivity in the tumor microenvironment are therefore expected to be highly warranted. In this study, intratumoral spatial cross presentation was investigated as a novel concept where immune cell composition in the tumor microenvironment was suggested to act as a proxy for immune surveillance. Double immunohistochemistry revealed a prognostic role of direct spatial interactions between CD11c+ antigen-presenting cells (APCs) and CD8+ cells in contrast to each marker alone in a soft tissue sarcoma (STS) cohort of 177 patients from the Karolinska University Hospital (MFS = 0.048, OS = 0.025). The survival benefit was verified in multivariable analysis (MFS = 0.012, OS = 0.004). Transcriptomics performed in the TCGA sarcoma cohort confirmed the prognostic value of combining CD11c with CD8 (259 patients, = 0.005), irrespective of levels and in a (PD-LI)-rich tumor microenvironment. Altogether, this study presents a histopathological approach to link immune surveillance and patient survival in STS. Notably, spatial cross presentation as a prognostic marker is distinct from therapy response-predictive biomarkers such as immune checkpoint molecules of the PD-L1/PD1 pathway.
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ISSN:2072-6694
2072-6694
DOI:10.3390/cancers13051175