The impact of sMICA/sMICB on immunochemotherapy outcomes in newly diagnosed diffuse large B-cell lymphoma

Sang Eun Yoon; Sujin Park; Junhun Cho; Kyung Ju Ryu; Booma Yandava; Sewon Lee; Seok Jin Kim; Won Seog Kim

doi:10.3389/fonc.2023.1194315

The impact of sMICA/sMICB on immunochemotherapy outcomes in newly diagnosed diffuse large B-cell lymphoma

Front Oncol. 2023 Nov 16:13:1194315. doi: 10.3389/fonc.2023.1194315. eCollection 2023.

Authors

Sang Eun Yoon^#¹, Sujin Park^#², Junhun Cho², Kyung Ju Ryu³, Booma Yandava⁴, Sewon Lee⁵, Seok Jin Kim¹, Won Seog Kim¹

Affiliations

¹ Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
² Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
³ Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Seoul, Republic of Korea.
⁴ Samyang Biopharm USA, Cambridge, MA, United States.
⁵ Division of Hematology-Oncology, Department of Internal Medicine, Ewha Womans University Mokdong Hospital, Seoul, Republic of Korea.

^# Contributed equally.

Abstract

Introduction: Soluble MHC class I-related chain A (sMICA) and B (sMICB) play a critical role tumor evolution and poor prognosis through an immune evasion mechanism. Thus, this study determines the interaction between sMICA/sMICB and the tumor immune environment in newly diagnosed diffuse large B-cell lymphoma (ND-DLBCL).

Methods: We analyzed sMICA/sMICB, cytokine in serum, and macrophage polarization analysis in tissue samples before the first chemotherapy administration. This research was performed to investigate the correlation between sMICA/sMICB expression and treatment outcomes as well as their influence on the immune system within ND-DLBCL.

Results: Of the 262 patients, 47.3% (n = 124) presented stage III or IV at diagnosis and 50.8% (n = 133) had a high International Prognostic Index (IPI ≥ 3). The patients with high (p = 0.034 and 0.004), elevated lactate dehydrogenase (p = 0.002 and 0.030), advanced stage (p = 0.003 and 0.012), and higher IPI risk (p = 0.009, and 0.032) correlated with the detection of sMICA or sMICB. The median progression-free survival (PFS) of patients with sMICA (p = 0.006) or sMICB (p =0.032) was inferior. Among the patients with advanced-stage or high IPI, those with sMICA or sMICB presented an inferior PFS and OS compared to those without. TNF-a, a pro-inflammatory cytokine, showed statistical significance with detected sMICA (p = 0.035) or sMICB (p = 0.044). Among anti-inflammatory cytokines, IL-1RA (P-value = 0.013) and IL-10 (p = 0.005) were associated with detecting sMICB, but not sMICA. In tissue samples, sMICA or sMICB detection did not correlate with the CD68/CD163 ratio.

Discussion: Conclusively, the identification of sMICA/sMICB presented unfavorable immunochemotherapy outcomes, and it was assumed that sMICA or sMICB and various cytokines interact, but the relationship with macrophage differentiation is unclear. Therefore, further research is needed to determine the relationship between sMICA/sMICB and tumor microenvironment in DLBCL.

Keywords: MHC class I-related chain A; MHC class I-related chain B; natural killer group 2 member D; newly diagnosed diffuse large B-cell lymphoma; tumor microenvironment.

Grants and funding

This research was supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute, funded by the Ministry of Health & Welfare, Republic of Korea (HR20C0025); a National Research Foundation of Korea grant funded by the Korean government (2022R1F1A1064058); a grant from the International Congress of Korean Society of Hematology (ICKSH) Research Project through the Korean Society of Hematology, Republic of Korea (grant No.: ICKSH-2022-05); and the Bio&Medical Technology Development Program of the National Research Foundation (NRF) funded by the Korean government (MSIT) (No. RS-2023-00222838).