CD74 and intratumoral immune response in breast cancer.

Zhi-Qiang Wang,Peter H. Watson,John R. Webb,Katy Milne

doi:10.18632/oncotarget.8610

Zhi-Qiang Wang, Peter H. Watson + Show 2 more

Open Access

https://doi.org/10.18632/oncotarget.8610

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Abstract

CD74 (invariant chain) plays a role in MHC class II antigen presentation. We assessed CD74 and MHCII expression in tumor cells, as well as CD8, CD4, and CD68 tumor infiltrating leucocyte (TIL) density by immunohistochemistry in a cohort of 492 breast cancer patients. CD74 expression was associated with poor prognostic markers including patient age, tumor grade, ER status, non-Luminal A subtypes, and with MHCII expression and higher TIL densities, particularly in the Basal-like subgroup. Univariate analysis showed a favorable prognostic effect of CD74 (Hazard ratio = 0.46, 95% CI = 0.26–0.89, p = 0.022) and for combined CD74/MHCII (Hazard ratio = 0.26, 95% CI = 0.17–0.81, p = 0.014) positive status for overall survival that was only manifested in the Basal-like subgroup. CD74 and MHCII expression is associated with patient survival in Basal-like breast cancer, and the association with TIL may reflect an effective intratumoral immune response.

Highlights

CD74 is expressed by breast tumor cells [1] as well as by several immune cell types
We have shown that CD74 expression is associated with better prognosis in Basal-like subtype invasive breast cancer
This association correlates with higher levels of MHCII expression by tumor cells and with a dense tumor infiltrating leucocyte (TIL) response

Summary

Introduction

CD74 (invariant chain, Li) is expressed by breast tumor cells [1] as well as by several immune cell types. CD74 has dual roles as a component of the MHC class II antigen presentation pathway and as a cytokine receptor [2], as well as intracellular effects on activation of transcription [3, 4]. Several previous studies based on mostly small cohorts have shown that CD74 is associated with ER negative and/or triple negative subgroups, but have been discordant with regard to the prognostic significance of CD74 [9, 10]. Given this dichotomy we set out to examine the relationship between CD74 and outcomes in breast cancer. We hypothesized that tumors that express CD74 along with MHCII, both key components of the antigen presenting machinery, represent those tumors most susceptible to a productive tumor infiltrating leukocyte (TIL) response and correspondingly good outcomes

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