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Multiplexed Immunofluorescence Analysis and Quantification of Intratumoral PD-1+ Tim-3+ CD8+ T Cells
Published on: February 8, 2018
CD74 and intratumoral immune response in breast cancer
Zhi-Qiang Wang1, Katy Milne1, John R Webb1
1Trev and Joyce Deeley Research Centre, British Columbia Cancer Agency, Victoria, British Columbia, Canada.
Insights
CD74 expression, along with MHC class II, is linked to patient survival in Basal-like breast cancer. Higher levels suggest a stronger immune response within the tumor, impacting overall survival rates.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- CD74, the invariant chain, is crucial for MHC class II antigen presentation.
- Understanding CD74 and MHC class II expression in breast cancer is vital for prognostic insights.
Purpose of the Study:
- To investigate the association between CD74 and MHC class II expression and tumor-infiltrating leukocyte (TIL) densities in breast cancer patients.
- To evaluate the prognostic significance of CD74 and MHC class II expression, individually and combined, on overall survival, particularly in the Basal-like subtype.
Main Methods:
- Immunohistochemistry was employed to assess CD74 and MHC class II expression in tumor cells.
- Density of CD8, CD4, and CD68 tumor-infiltrating leukocytes was quantified.
- Analysis included a cohort of 492 breast cancer patients, with subgroup analysis for Basal-like cancers.
Main Results:
- CD74 expression correlated with adverse prognostic markers (age, grade, ER status, non-Luminal A subtypes).
- CD74 and MHC class II expression were associated with higher TIL densities, especially in Basal-like breast cancer.
- Favorable overall survival was observed for CD74-positive and combined CD74/MHC class II-positive status, specifically within the Basal-like subgroup (HR=0.46, p=0.022 and HR=0.26, p=0.014, respectively).
Conclusions:
- CD74 and MHC class II expression are significant prognostic indicators in Basal-like breast cancer.
- The association between CD74/MHC class II expression and TILs may indicate an effective anti-tumor immune response.
- These findings highlight the potential role of CD74 and MHC class II in immune-mediated breast cancer survival.
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.

