Clinical Significance of Expression of Immunoadjuvant Molecules (LAG-3, TIM-3, OX-40) in Neoadjuvant Chemotherapy for Breast Cancer.

Abstract

BACKGROUND/AIM:

Various immunosuppressive factors that inhibit the immune response to cancer are present in cancer cells and the cancer microenvironment. Co-inhibitory and co-stimulatory receptors are dynamically expressed on T-cells as immunoadjuvant molecules that regulate the state of T-cell activity. In this report we focus on immunoadjuvant molecules such as LAG-3, TIM-3, and OX-40, for which there have been few published reports. We investigated the expression of LAG-3, TIM-3 and OX-40 in tumor-infiltrating lymphocytes (TILs), and clinically verified the significance of that expression in relation to neoadjuvant thermotherapy (NAC).

PATIENTS AND METHODS:

A total of 177 patients with resectable early-stage breast cancer were treated with NAC. Estrogen receptor (ER), progesterone receptor (PgR), human epidermal growth factor receptor 2 (HER2), Ki67, LAG-3, TIM-3 and OX-40 status were assessed by immunohistochemistry.

RESULTS:

The group with low-LAG-3 expression was significantly smaller than the group with high expression in triple-negative breast cancer (TNBC) (p=0.038) and HER2-enriched breast cancer (HER2BC) (p=0.021), while the total number of pathological complete response (pCR) patients was greater (p<0.001). In TNBC and HER2BC, the pCR rate was significantly higher in the low-LAG-3 expression group than in the high-LAG-3 expression group (p<0.001 and p=0.02, respectively). Moreover, on multivariate analysis low-LAG-3 expression status was an independent predictor of favorable prognosis (TNBC: p=0.014, HR=8.124; HER2BC: p=0.048, HR=10.400).

CONCLUSION:

Our findings suggest that LAG-3 may become a biomarker in highly malignant breast cancers such as TNBC and HER2BC that can predict the therapeutic efficacy of NAC.

• Authors: Yuka Asano, Shinichiro Kashiwagi, Koji Takada, Sae Ishihara, Wataru Goto, Tamami Morisaki, Masatsune Shibutani, Hiroaki Tanaka, Kosei Hirakawa, Masaichi Ohira
• Journal: Anticancer research (Anticancer Res) Vol. 42 Issue 1 Pg. 125-136 (Jan 2022) ISSN: 1791-7530 [Electronic] Greece
• PMID: 34969718 (Publication Type: Journal Article)
• Copyright: Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Chemical References

• Adjuvants, Immunologic

Topics

• Adjuvants, Immunologic (pharmacology, therapeutic use)
• Breast Neoplasms (drug therapy, pathology)
• Female
• Humans
• Immunohistochemistry
• Neoadjuvant Therapy (methods)
• Prognosis