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1763 Ratio of Circulating CD8+ T Lymphocytes to M-MDSCs (CD8MMR): A Novel Prognostic Predictor for Treatment-Naïve DLBCL Patients

Program: Oral and Poster Abstracts
Session: 627. Aggressive Lymphomas: Clinical and Epidemiological: Poster I
Hematology Disease Topics & Pathways:
adult, Research, Lymphomas, non-Hodgkin lymphoma, epidemiology, B Cell lymphoma, health outcomes research, Clinical Research, Diseases, aggressive lymphoma, Lymphoid Malignancies, survivorship, Study Population, Human
Saturday, December 9, 2023, 5:30 PM-7:30 PM

Hao-Yuan Wang, MD1, Fu-Chen Yang, PhD2*, Ching-Fen Yang, MD3*, Chun-Kuang Tsai, MD1*, Po-Shen Ko, MD1*, Yao-Chung Liu, MD1* and Nien-Jung Chen, PhD2*

1Division of Hematology and Oncology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
2Institute of Microbiology and Immunology, National Yang Ming Chiao Tung University, Taipei, Taiwan
3Department of Pathology and Laboratory Medicine, Taipei Veterans General Hospital, Taipei, Taiwan


CD8+ T lymphocytes are crucial in contemporary cell-and-immunotherapies as they can be functionally enhanced or manipulated. Monocytic myeloid-derived suppressor cells (M-MDSCs) are known for their intense immunosuppressive ability, and higher percentages of circulating M-MDSCs among peripheral-blood monocytes or white cells are associated with a worse prognosis. Recently, a low lymphocyte-to-monocyte ratio (LMR) has been linked to a poor prognosis in lymphoma patients. Consequently, we hypothesized that the ratio of circulating CD8+ T lymphocytes to M-MDSCs (CD8MMR) could be a novel and more precise predictor for the clinical outcomes of DLBCL patients before initiating treatment.


This prospective, observational study enrolled 136 adults with treatment-naïve DLBCL from May 2019 to March 2023 in a tertiary medical center in Taiwan. Patients with primary CNS lymphoma or primary mediastinal B-cell lymphoma were excluded. Fresh peripheral blood samples were obtained to calculate the absolute counts of CD8+ T lymphocytes and M-MDSCs, defined as alive singlets with CD45+ CD3+ CD8+ and CD45+ CD15- CD14+ CD11b+ CD33+ HLA-DRlow/- by flow cytometry, respectively. ROC analysis and AUC determined the cut-off values for LMR and CD8MMR.


For 136 treatment-naïve DLBCL patients, the median age was 70, with 61.8% being male. Among them, 37.5% were in stage IV, and 27.9% were classified as the germinal-center B-cell (GCB) subtype by IHC staining according to the Hans algorithm. Additionally, 43.4% were diagnosed with double expressor lymphoma (DEL). The IPI risk score distribution was as follows: 7.4%, 18.4%, 17.6%, 24.3%, 19.9%, and 12.5% were in scores 0, 1, 2, 3, 4, and 5, respectively. Of note, the median level of LMR was 2.17, the median level of absolute counts of circulating CD8+ T lymphocytes was 385/µL, the median level of absolute counts of circulating M-MDSCs was 102/µL, and the median level of CD8MMR was 3.56.

DLBCL patients with high-risk IPI had a significantly lower CD8MMR than patients with intermediate or low-risk IPI (1.34 vs. 4.51 vs. 7.82, P H vs. L = 0.001, P H vs. I = 0.060, P I vs. L = 0.082). DLBCL patients with the non-GCB subtype (2.75 vs. 5.63, P = 0.031) also demonstrated a significantly lower CD8MMR. Additionally, there were trends of lower CD8MMR in elderly patients > 70 (2.74 vs. 3.91, P = 0.209) and patients with DEL (3.33 vs. 4.65, P = 0.101).

After a median follow-up of 22.6 months for the 136 DLBCL patients, LMR was at first tested, and patients with LMR < 1.19 had significantly worse PFS (13.8 months vs. non-reach, Log Rank P = 0.004) and OS (non-reach vs. non-reach, Log Rank P = 0.019) than those with LMR 1.19. Next, we examined the CD8MMR, and patients with CD8MMR < 4.40 experienced significantly worse PFS (21.3 months vs. non-reach, Log Rank P < 0.001) and OS (non-reach vs. non-reach, Log Rank P < 0.001) compared to those with CD8MMR 4.40 [Figure].

We subsequently conducted a multivariate Cox regression analysis to validate whether CD8MMR < 4.40 could serve as an independent predictor of poor prognosis [Table]. The results showed that "CD8MMR < 4.40" was confirmed as an independent prognostic factor for both PFS (HR = 2.747; 95% CI = 1.275 to 5.918; P = 0.010) and OS (HR = 3.669; 95% CI = 1.462 to 9.211; P = 0.006) after adjusting for confounding factors, including age, sex, IPI risk scores, bulky mass > 10 cm, non-GCB type, DEL, and LMR < 1.19.

In this study cohort, 106 (77.9%) patients received R-CHOP-like regimens as induction therapies, 25 (18.4%) patients received an R-EPOCH regimen, two (1.5%) patients received an R-HyperCVAD regimen, and three (2.2%) patients died before completing the first cycle of chemoimmunotherapy. Among the 106 DLBCL patients receiving R-CHOP-like regimens, 57 patients showed CD8MMR < 4.40 and reported a significantly lower rate of complete remission (73.7% vs. 95.9%, P = 0.006) at the end of induction therapy compared to the 49 patients with CD8MMR 4.40. Furthermore, patients with CD8MMR < 4.40 had significantly worse PFS (17.4 months vs. non-reach, P < 0.001) and OS (non-reach vs. non-reach, P < 0.001) compared to those with CD8MMR 4.40.


A low ratio of circulating CD8+ T lymphocytes to M-MDSCs (CD8MMR) serves as a poor prognostic factor for both PFS and OS in treatment-naïve DLBCL patients. This finding warrants further investigation and highlights the possibility of risk-adapted strategies when treating DLBCL patients.

Disclosures: No relevant conflicts of interest to declare.

*signifies non-member of ASH