Objective: To investigate the expression of Schlafen family member 11 (SLFN11) in breast cancer and its correlation with the expression of immune escape related molecules. Methods: TCGA and TIMER 2.0 databases were used to predict the expression of SLFN11 in tumors. TIMER 2.0 was used to predict the relationship between SLFN11 and immune cell infiltration. The effects of SLFN11 on the expression of immune cells, immunosuppressive agents and immunopotentiators in breast cancer were analyzed by TISIDB database. The expression of SLFN11 mRNA in breast cancer cell lines was detected by qRT-PCR. Results: The expression of SLFN11 was down-regulated in breast cancer, which was associated with TP53 mutation and SLFN11 promoter methylation. TIMER 2.0 database predicted that the expression of SLFN11 in breast cancer was related to the infiltration of B cells, CD8+ cells and CD4+ cells. The TISIDB database predicted that the expression of SLFN11 was positively correlated with lymphocytes such as TH1, NKT and TfH (P＜0.05), positively correlated with immunosuppressive molecules such as PDCD1LG2, CD96 and TIGT (P＜0.05), and positively correlated with the expression of major histocompatibility complex (MHC) molecules such as LA-DRA, HLA-DMB and HLA-DOA (P＜0.05). Quantitative analysis showed that compared with normal breast cells, the expression of SLFN11 in breast cancer cells was down-regulated (P＜0.01), and SLFN11 in paclitaxel-resistant cells was lower than that in corresponding breast cancer parent cells (P＜0.05). Conclusion: The expression of SLFN11 is down-regulated in invasive breast cancer, which is related to the number of lymphocytes, immune cell infiltration and the expression of immunosuppressive molecules.
WU Qiong
,
LIU Zixuan
,
SHI Yurong
. Expression of SLFN11 in breast cancer and its correlation with immune escape[J]. Journal of Baotou Medical College, 2026
, 42(4)
: 55
-60
.
DOI: 10.16833/j.cnki.jbmc.2026.04.009
[1] 世界癌症日: 乳腺癌超肺癌成全球第一大癌[J]. 临床研究, 2021, 29(2): 4.
[2] Mu Y, Lou J, Srivastava M, et al. SLFN11 inhibits checkpoint maintenance and homologous recombination repair[J]. EMBO Rep, 2016, 17(1): 94-109.
[3] Masuda K, Yoshida T, Motoi N, et al. Schlafen 11 expression in patients with small cell lung cancer and its association with clinical outcomes[J]. Thorac Cancer, 2025, 16(1): e15529.
[4] Zhou J, Zhang MY, Gao AA, et al. Epigenetic silencing schlafen-11 sensitizes esophageal cancer to ATM inhibitor[J]. World J Gastrointest Oncol, 2024, 16(5): 2060-2073.
[5] Kundu K, Cardnell RJ, Zhang B, et al. SLFN11 biomarker status predicts response to lurbinectedin as a single agent and in combination with ATR inhibition in small cell lung cancer[J]. Transl Lung Cancer Res, 2021, 10(11): 4095-4105.
[6] Zhou C, Weng J, Liu C, et al. Disruption of SLFN11 deficiency-induced CCL2 signaling and macrophage m2 polarization potentiates Anti-PD-1 therapy efficacy in hepatocellular carcinoma[J]. Gastroenterology, 2023, 164(7): 1261-1278.
[7] Li M, Kao E, Gao X, et al. Codon-usage-based inhibition of HIV protein synthesis by human schlafen 11[J]. Nature, 2012, 491(7422): 125-128.
[8] Murai Y, Jo U, Murai J, et al. SLFN11 inactivation induces proteotoxic stress and sensitizes cancer cells to ubiquitin activating enzyme inhibitor TAK-243[J]. Cancer Res, 2021, 81(11): 3067-3078.
[9] Nogales V, Reinhold WC, Varma S, et al..Epigenetic inactivation of the putative DNA/RNA helicase SLFN11 in human cancer confers resistance to platinum drugs[J]. Oncotarget, 2016, 7(3): 3084-97.
[10] Tang SW, Thomas A, Murai J, et al. Overcoming resistance to DNA-targeted agents by epigenetic activation of Schlafen 11 (SLFN11) expression with class I histone deacetylase inhibitors[J]. Clinical Cancer Research, 2018, 24(8): 1944-1953.
[11] Zhou C, Weng J, Liu C, et al. Disruption of SLFN11 deficiency-induced CCL2 signaling and macrophage M2 polarization potentiates Anti-PD-1 therapy efficacy in hepatocellular carcinoma[J]. Gastroenterology, 2023, 164(7): 1261-1278.
[12] Mezzadra R, de Bruijn M, Jae LT, et al. SLFN11 can sensitize tumor cells towards IFN-γ-mediated T cell killing[J]. PLoS One, 2019, 14(2): e0212053.
[13] Yang Y, Wang X, Bai Y, et al. Programmed death-ligand 2(PD-L2) expression in bladder cancer[J]. Urol Oncol, 2020, 38(6): 603.
[14] Bradbury A, Hall S, Curtin N, et al. Targeting ATR as cancer therapy:A new era for synthetic lethality and synergistic combinations[J]. Pharmacology & Therapeutics, 2020, 207: 107450.
[15] Li M, Kao E, Malone D, et al. DNA damage-induced cell death relies on SLFN11 dependent cleavage of distinct type II tRNAs[J]. Nature Structural & Molecular Biology, 2018, 25(11):1047-1058.
[16] Coussy F, El-botty R, Château-Joubert S, et al. BRCAness, SLFN11, and RB1 loss predict response to topoisomerase I inhibitors in triple-negative breast cancers[J]. Science Translational Medicine, 2020, 12(531): eaax2625.
