American Association for Cancer Research
10780432ccr190285-sup-215982_3_supp_5813159_pysghc.xlsx (116.56 kB)

Cox regression of individual genes related to T cell evasion from Clonality, Antigen Recognition, and Suppression of CD8+ T Cells Differentially Affect Prognosis of Breast Cancer Subtypes

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posted on 2023-03-31, 21:32 authored by Dora Hammerl, Maarten P.G. Massink, Marcel Smid, Carolien H.M. van Deurzen, Hanne E.J. Meijers-Heijboer, Quinten Waisfisz, Reno Debets, John W.M. Martens

Univariate cox-regression analysis of genes related to T cell evasion per molecular subtype (with MFS)


Dutch Cancer Society



In breast cancer, response rates to immune therapies are generally low and differ significantly across molecular subtypes, urging a better understanding of immunogenicity and immune evasion. We interrogated large gene-expression data sets including 867 node-negative, treatment-naïve breast cancer patients (microarray data) and 347 breast cancer patients (whole-genome sequencing and transcriptome data) according to parameters of T cells as well as immune microenvironment in relation to patient survival. We developed a 109–immune gene signature that captures abundance of CD8 tumor-infiltrating lymphocytes (TIL) and is prognostic in basal-like, her2, and luminal B breast cancer, but not in luminal A or normal-like breast cancer. Basal-like and her2 are characterized by highest CD8 TIL abundance, highest T-cell clonality, highest frequencies of memory T cells, and highest antigenicity, yet only the former shows highest expression level of immune and metabolic checkpoints and highest frequency of myeloid suppressor cells. Also, luminal B shows a high antigenicity and T-cell clonality, yet a low abundance of CD8 TILs. In contrast, luminal A and normal-like both show a low antigenicity, and notably, a low and high abundance of CD8 TILs, respectively, which associates with T-cell influx parameters, such as expression of adhesion molecules. Collectively, our data argue that not only CD8 T-cell presence itself, but rather T-cell clonality, T-cell subset distribution, coinhibition, and antigen presentation reflect occurrence of a CD8 T-cell response in breast cancer subtypes, which have been aborted by distinct T-cell–suppressive mechanisms, providing a rationale for subtype-specific combination immune therapies.