Recent Research and Clinical Progress of CTLA-4-based Immunotherapy for Breast Cancer

Overview

Journal Front Oncol

Specialty Oncology

Date 2023 Oct 20

PMID 37860188

Authors

Hongsheng Zhang

Jintao Mi

Qi Xin

Weiwei Cao

Chunjiao Song

Naidan Zhang

Chengliang Yuan

Affiliations

Soon will be listed here.

Abstract

Breast cancer is characterized by a high incidence rate and its treatment challenges, particularly in certain subtypes. Consequently, there is an urgent need for the development of novel therapeutic approaches. Immunotherapy utilizing immune checkpoint inhibitors (ICIs) is currently gaining momentum for the treatment of breast cancer. Substantial progress has been made in clinical studies employing cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) inhibitors for breast cancer, but the cure rates are relatively low. To improve the efficacy of CTLA-4-based therapy for breast cancer, further research is imperative to explore more effective immune-based treatment strategies. In addition to monotherapy, CTLA-4 inhibitors are also being investigated in combination with other ICIs or alternative medications. However, it should be noted that immune-based treatments may cause adverse events. This review focuses on the mechanisms of CTLA-4 inhibitor monotherapy or combination therapy in breast cancer. We systematically summarize the latest research and clinical advances in CTLA-4-based immunotherapy for breast cancer, providing new perspectives on the treatment of breast cancer. In addition, this review highlights the immune-related adverse events (irAEs) associated with CTLA-4 inhibitors, providing insights into the development of appropriate clinical tumor immunotherapy regimens and intervention strategies.

Citing Articles

Divide and Conquer-Targeted Therapy for Triple-Negative Breast Cancer.

Nedeljkovic M, Vuletic A, Mirjacic Martinovic K Int J Mol Sci. 2025; 26(4).

PMID: 40003864 PMC: 11855393. DOI: 10.3390/ijms26041396.

Brd7 loss reawakens dormant metastasis initiating cells in lung by forging an immunosuppressive niche.

Mondal J, Zhang J, Qing F, Li S, Kumar D, Huse J Nat Commun. 2025; 16(1):1378.

PMID: 39910049 PMC: 11799300. DOI: 10.1038/s41467-025-56347-2.

CD8 T cell exhaustion in the tumor microenvironment of breast cancer.

Xie H, Xi X, Lei T, Liu H, Xia Z Front Immunol. 2024; 15:1507283.

PMID: 39717767 PMC: 11663851. DOI: 10.3389/fimmu.2024.1507283.

Current applications of tumor local ablation (TLA) combined with immune checkpoint inhibitors in breast cancer treatment.

Tang L, Wang D, Hu T, Lin X, Wu S Cancer Drug Resist. 2024; 7:33.

PMID: 39403601 PMC: 11472568. DOI: 10.20517/cdr.2024.77.

Bridging the Gap: Immune Checkpoint Inhibitor as an Option in the Management of Advanced and Recurrent Cervical Cancer in Sub-Saharan Africa.

Okpalanwaka I, Anazodo F, Chike-Aliozor Z, Ekweozor C, Ochie K, Oboh O Cureus. 2024; 16(9):e69136.

PMID: 39398762 PMC: 11467442. DOI: 10.7759/cureus.69136.

References

Yan W, Khan M, Wu X, Simone 2nd C, Fan J, Gressen E . Spatially fractionated radiation therapy: History, present and the future. Clin Transl Radiat Oncol. 2019; 20:30-38. PMC: 6872856. DOI: 10.1016/j.ctro.2019.10.004. View

Iyengar N, Jones L . Development of Exercise as Interception Therapy for Cancer: A Review. JAMA Oncol. 2019; 5(11):1620-1627. PMC: 7542631. DOI: 10.1001/jamaoncol.2019.2585. View

Rodriguez-Ruiz M, Vanpouille-Box C, Melero I, Formenti S, Demaria S . Immunological Mechanisms Responsible for Radiation-Induced Abscopal Effect. Trends Immunol. 2018; 39(8):644-655. PMC: 6326574. DOI: 10.1016/j.it.2018.06.001. View

Chen X, Shao Q, Hao S, Zhao Z, Wang Y, Guo X . CTLA-4 positive breast cancer cells suppress dendritic cells maturation and function. Oncotarget. 2017; 8(8):13703-13715. PMC: 5355131. DOI: 10.18632/oncotarget.14626. View

Berraondo P, Sanmamed M, Ochoa M, Etxeberria I, Aznar M, Perez-Gracia J . Cytokines in clinical cancer immunotherapy. Br J Cancer. 2018; 120(1):6-15. PMC: 6325155. DOI: 10.1038/s41416-018-0328-y. View

Hassan R, Miller A, Sharon E, Thomas A, Reynolds J, Ling A . Major cancer regressions in mesothelioma after treatment with an anti-mesothelin immunotoxin and immune suppression. Sci Transl Med. 2013; 5(208):208ra147. PMC: 6369691. DOI: 10.1126/scitranslmed.3006941. View

Chafe S, McDonald P, Saberi S, Nemirovsky O, Venkateswaran G, Burugu S . Targeting Hypoxia-Induced Carbonic Anhydrase IX Enhances Immune-Checkpoint Blockade Locally and Systemically. Cancer Immunol Res. 2019; 7(7):1064-1078. DOI: 10.1158/2326-6066.CIR-18-0657. View

Stylianopoulos T, Jain R . Combining two strategies to improve perfusion and drug delivery in solid tumors. Proc Natl Acad Sci U S A. 2013; 110(46):18632-7. PMC: 3832007. DOI: 10.1073/pnas.1318415110. View

Iwata T, Ishii C, Ishida S, Ogitani Y, Wada T, Agatsuma T . A HER2-Targeting Antibody-Drug Conjugate, Trastuzumab Deruxtecan (DS-8201a), Enhances Antitumor Immunity in a Mouse Model. Mol Cancer Ther. 2018; 17(7):1494-1503. DOI: 10.1158/1535-7163.MCT-17-0749. View

10.

Yang F, Shay C, Abousaud M, Tang C, Li Y, Qin Z . Patterns of toxicity burden for FDA-approved immune checkpoint inhibitors in the United States. J Exp Clin Cancer Res. 2023; 42(1):4. DOI: 10.1186/s13046-022-02568-y. View

11.

Grubczak K, Kretowska-Grunwald A, Groth D, Poplawska I, Eljaszewicz A, Bolkun L . Differential Response of MDA-MB-231 and MCF-7 Breast Cancer Cells to In Vitro Inhibition with CTLA-4 and PD-1 through Cancer-Immune Cells Modified Interactions. Cells. 2021; 10(8). PMC: 8392578. DOI: 10.3390/cells10082044. View

12.

Hamzah J, Jugold M, Kiessling F, Rigby P, Manzur M, Marti H . Vascular normalization in Rgs5-deficient tumours promotes immune destruction. Nature. 2008; 453(7193):410-4. DOI: 10.1038/nature06868. View

13.

Li Y, Li X, Doughty A, West C, Wang L, Zhou F . Phototherapy using immunologically modified carbon nanotubes to potentiate checkpoint blockade for metastatic breast cancer. Nanomedicine. 2019; 18:44-53. PMC: 7063973. DOI: 10.1016/j.nano.2019.02.009. View

14.

Zhang H, Xie W, Zhang Y, Dong X, Liu C, Yi J . Oncolytic adenoviruses synergistically enhance anti-PD-L1 and anti-CTLA-4 immunotherapy by modulating the tumour microenvironment in a 4T1 orthotopic mouse model. Cancer Gene Ther. 2021; 29(5):456-465. PMC: 9113929. DOI: 10.1038/s41417-021-00389-3. View

15.

King D, Albertini M, Schalch H, Hank J, Gan J, Surfus J . Phase I clinical trial of the immunocytokine EMD 273063 in melanoma patients. J Clin Oncol. 2004; 22(22):4463-73. PMC: 2367368. DOI: 10.1200/JCO.2004.11.035. View

16.

Leshem Y, King E, Mazor R, Reiter Y, Pastan I . SS1P Immunotoxin Induces Markers of Immunogenic Cell Death and Enhances the Effect of the CTLA-4 Blockade in AE17M Mouse Mesothelioma Tumors. Toxins (Basel). 2018; 10(11). PMC: 6265743. DOI: 10.3390/toxins10110470. View

17.

van Weverwijk A, de Visser K . Mechanisms driving the immunoregulatory function of cancer cells. Nat Rev Cancer. 2023; 23(4):193-215. DOI: 10.1038/s41568-022-00544-4. View

18.

Kalbasi A, Ribas A . Tumour-intrinsic resistance to immune checkpoint blockade. Nat Rev Immunol. 2019; 20(1):25-39. PMC: 8499690. DOI: 10.1038/s41577-019-0218-4. View

19.

Blomberg O, Kos K, Spagnuolo L, Isaeva O, Garner H, Wellenstein M . Neoadjuvant immune checkpoint blockade triggers persistent and systemic T activation which blunts therapeutic efficacy against metastatic spread of breast tumors. Oncoimmunology. 2023; 12(1):2201147. PMC: 10114978. DOI: 10.1080/2162402X.2023.2201147. View

20.

Qu Q, Zhai Z, Xu J, Li S, Chen C, Lu B . IL36 Cooperates With Anti-CTLA-4 mAbs to Facilitate Antitumor Immune Responses. Front Immunol. 2020; 11:634. PMC: 7174717. DOI: 10.3389/fimmu.2020.00634. View