Targeting the CD47/SIRPα interaction in cancer - opportunities in non-Hodgkin lymphoma

Sep 22, 2026

Uploaded by Aran

Macrophages serve as attractive targets for novel cancer immunotherapy because they infiltrate the tumor microenvironment and can engulf and destroy cancer cells via phagocytosis. The CD47/SIRPα axis functions as a key immune checkpoint governing macrophage attack on cancer cells and has been actively studied preclinically and clinically. The review evaluates the rationale for CD47/SIRPα-targeting therapies, summarizes recent lymphoma trial outcomes, highlights efficacy markers, and discusses combination strategies and challenges such as hematologic on-target toxicity and antigen sink effects.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages15

Reading Time38 min

AccessFree to download

Introduction

CD47/SIRPα as an immune checkpoint in macrophage targeting

Rationale for CD47/SIRPα-targeting therapies

Clinical evidence in non-Hodgkin lymphoma

Combination strategies and efficacy signals

Key challenges and limitations

Expert opinion

Author Manuscript Author Manuscript Author Manuscript Author Manuscript | | HHS Public Access
Author manuscript
Expert Opin Investig Drugs. Author manuscript; available in PMC 2026 June 22. | | --- | --- | Published in final edited form as: Expert Opin Investig Drugs. 2026 April ; 35(4): 265–272. doi:10.1080/13543784.2026.2643307 . Targeting the CD47/SIRPα interaction in cancer: opportunities in non-Hodgkin lymphoma Carlota Pagès-Gelia,b, Kipp Weiskopfa,b,c a Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA b Department of Medicine, Harvard Medical School, Boston, MA, USAc Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA Abstract Introduction: Macrophages are attractive targets for novel cancer immunotherapy approaches since they can infiltrate into the tumor microenvironment and have the capacity to engulf and destroy cancer cells by phagocytosis. The CD47/SIRPα axis is a key immune checkpoint that regulates macrophages’ ability to attack cancer cells and has been the subject of intense preclinical and clinical investigation. Areas covered: We review the scientific rationale for developing CD47/SIRPα-targeting therapies, and we summarize results of recent clinical trials that tested anti-CD47 antibodies, SIRPα-Fc fusion proteins, or anti-SIRPα antibodies in patients with lymphoma. We review signs of efficacy, opportunities for combination strategies, and challenges such as on-target hematologic toxicity and an ‘antigen sink’ that exists due to CD47 expression on blood cells. Expert opinion: Multiple CD47/SIRPα-targeting therapeutics and multiple clinical trials have demonstrated encouraging results in patients with non-Hodgkin lymphoma, where objective responses have been observed in combination with rituximab and other anti-cancer agents. Nextgeneration approaches, such as bispecific antibodies and engineering efforts to reduce blood cell This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License ([https://creativecommons.org/licenses/by-nc-nd/4.0/](https://creativecommons.org/licenses/by-nc-nd/4.0/)), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited, and is not altered, transformed, or built upon in any way. The terms on which this article has been published allow the posting of the Accepted Manuscript in a repository by the author(s) or with their consent. CONTACT Kipp Weiskopfkweiskop@bidmc.harvard.edu Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA 02115, USA. Reviewer disclosures Peer reviewers on this manuscript have no relevant financial or other relationships to disclose. Disclosures of interest C Pagès-Geli and K Weiskopf have filed U.S. patent applications related to this work, and K Weiskopfis an inventor of intellectual property pertaining to magrolimab and evorpacept. K Weiskopf reports patents/royalties (Stanford University, Whitehead Institute, Forty Seven, Gilead Sciences, ALX Oncology, DEM Biopharma, Inograft, Bitterroot Bio); co-founder, past or present scientific advisory board member, and equity holder (ALX Oncology, DEM Biopharma, Solu Therapeutics), stock ownership (Ginkgo Bioworks) . Declaration of generative AI in scientific writing During the preparation of this work, the authors used Chat GPT exclusively for minor grammatical corrections in this work. All sentences revised by ChatGPT were reviewed and verified by the authors. No content was generated by the Chat GPT or any other AI service. Author Manuscript Author Manuscript Author Manuscript Author Manuscript Pagès-Geli and Weiskopf Page 2 binding, are now under clinical development and may be successful strategies to unlock the extraordinary potential of the CD47/SIRPα immune checkpoint. Keywords Macrophage immunotherapy; CD47/SIRPα axis blockade; B-cell lymphoma; a

FAQs

Why are macrophages considered promising targets for cancer immunotherapy?

Macrophages infiltrate the tumor microenvironment and can destroy cancer cells through phagocytosis. This makes them useful effector cells when appropriately activated or unblocked.

What role does the CD47/SIRPα axis play in cancer immune evasion?

The CD47/SIRPα pathway regulates macrophages’ ability to attack cancer cells and functions as an immune checkpoint. Blocking this axis can restore macrophage-mediated anti-tumor activity.

What challenges and limitations are discussed for CD47/SIRPα-targeting therapies in lymphoma?

The review highlights on-target hematologic toxicity and an “antigen sink” effect due to CD47 expression on blood cells. It also discusses the need to optimize strategies, including combination approaches, to improve outcomes.

Sep 22, 2026

Uploaded by Aran