Th2 cell infiltrations predict neoadjuvant chemotherapy response of estrogen receptor-positive breast cancer

Lan Le; Yoshihisa Tokumaru; Masanori Oshi; Mariko Asaoka; Li Yan; Itaru Endo; Takashi Ishikawa; Manabu Futamura; Kazuhiro Yoshida; Kazuaki Takabe

doi:10.21037/gs-20-571

Th2 cell infiltrations predict neoadjuvant chemotherapy response of estrogen receptor-positive breast cancer

Gland Surg. 2021 Jan;10(1):154-165. doi: 10.21037/gs-20-571.

Authors

Lan Le^{1

2}, Yoshihisa Tokumaru^{1

3}, Masanori Oshi^{1

4}, Mariko Asaoka^{1

5}, Li Yan⁶, Itaru Endo⁴, Takashi Ishikawa⁵, Manabu Futamura³, Kazuhiro Yoshida³, Kazuaki Takabe^{1

2

4

5

7

8}

Affiliations

¹ Breast Surgery, Department of Surgical Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA.
² Department of Surgery, University at Buffalo Jacobs School of Medicine and Biomedical Sciences, The State University of New York, Buffalo, NY, USA.
³ Department of Surgical Oncology, Graduate School of Medicine, Gifu University, Gifu, Japan.
⁴ Department of Gastroenterological Surgery, Yokohama City University, Yokohama, Japan.
⁵ Department of Breast Surgery and Oncology, Tokyo Medical University, Tokyo, Japan.
⁶ Department of Biostatistics & Bioinformatics, Roswell Park Cancer Institute, Buffalo, NY, USA.
⁷ Department of Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
⁸ Department of Breast Surgery, Fukushima Medical University School of Medicine, Fukushima, Japan.

Abstract

Background: High infiltration of Th2 is linked to breast cancer progression and metastasis through the induction of cytokine release and T-cell anergy. The estrogen receptor (ER)-positive subtype, which accounts for 70% of breast cancer, is known to respond less to neoadjuvant chemotherapy (NAC) due to its low potential for proliferation. We hypothesized that Th2 high tumors are highly proliferative, and thus more likely to respond to NAC in ER-positive breast cancer.

Methods: We obtained clinicopathological data and overall survival information on 1,069 breast cancer patients from The Cancer Genome Atlas (TCGA). Computational algorithms and CIBERSORT were used to estimate immune cell infiltration. Additionally, xCell was used for validation.

Results: Th2 high tumors did not consistently associate with an unfavorable immune cell composition and tumor immune microenvironment but were found to be significantly elevated in the cancer stage. Th2 high tumors also correlated with high Nottingham pathological grade, as well as with Ki-67 and proliferation score in ER-positive subtypes. High Th2 tumors achieved a pathological complete response (pCR) significantly higher in ER-positive breast cancer.

Conclusions: In conclusion, high levels of Th2 are associated with aggressive features of breast cancer. Th2 levels may be a biomarker in patient selection for NAC in ER-positive breast cancer.

Keywords: ER positive; Th2; breast cancer; tumor immune microenvironment; type 2 helper T cells.