Opportunities and challenges of CD47-targeted therapy in cancer immunotherapy

Abstract

Cancer immunotherapy has emerged as a promising strategy for the treatment of cancer, with the tumor microenvironment (TME) playing a pivotal role in modulating the immune response. CD47, a cell surface protein, has been identified as a crucial regulator of the TME and a potential therapeutic target for cancer therapy. However, the precise functions and implications of CD47 in the TME during immunotherapy for cancer patients remain incompletely understood. This comprehensive review aims to provide an overview of CD47's multifaced role in TME regulation and immune evasion, elucidating its impact on various types of immunotherapy outcomes, including checkpoint inhibitors and CAR T-cell therapy. Notably, CD47-targeted therapies offer a promising avenue for improving cancer treatment outcomes, especially when combined with other immunotherapeutic approaches. The review also discusses current and potential CD47-targeted therapies being explored for cancer treatment and delves into the associated challenges and opportunities inherent in targeting CD47. Despite the demonstrated effectiveness of CD47-targeted therapies, there are potential problems, including unintended effects on healthy cells, hematological toxicities, and the development if resistance. Consequently, further research efforts are warranted to fully understand the underlying mechanisms of resistance and to optimize CD47-targeted therapies through innovative combination approaches, ultimately improving cancer treatment outcomes. Overall, this comprehensive review highlights the significance of CD47 as a promising target for cancer immunotherapy and provides valuable insight into the challenges and opportunities in developing effective CD47-targeted therapies for cancer treatment.

The Immune Response of Cancer Cells in Breast and Gynecologic Neoplasms

“…It has been discovered that a variety of cancer cells present high expression level of CD47 which correlates with poor prognosis of the disease. CD47 is overexpressed in various gynecological cancers such as ovarian and endometrial cancers, contributing to immune evasion by inhibiting macrophage phagocytosis of cancer cells [ 123 ]. Especially in regard to ovarian cancer, squamous cell carcinoma of the head and neck, gliomas, osteosarcoma, and melanoma [ 124 , 125 , 126 , 127 , 128 ].…”

“…A similar result was observed with KWAR23—SIRPα specific monoclonal antibody that disrupted SIRPα-CD47 interaction [ 145 ]. Considering the clinical trials, which are currently exploring anti-CD47 antibodies against ovarian cancer, they aim to block this signal and enhance the immune system’s ability to eliminate cancer cells, offering a promising therapeutic strategy [ 123 , 146 ].…”

Engineering Exosomes for Therapeutic Applications: Decoding Biogenesis, Content Modification, and Cargo Loading Strategies

“…Additionally, administering erythropoietin alongside the treatment can be beneficial in managing these effects in clinical settings. 120 …”

The advances in targeting CD47/SIRPα “do not eat me” axis and their ongoing challenges as an anticancer therapy

“…In a review article, Hua Yang and colleagues describe the current landscape and future prospects of CD47-based immunotherapy for hematological malignancies [ 31 ]. While CD47 blocking antibodies have shown success in hematological malignancies as monotherapy [ 32 ], their efficacy in monotherapy may be limited in solid tumors due to the heterogeneity and complexity of the TME [ 33 ]. Therefore, combination therapies are being evaluated to potentiate anti-CD47 immunotherapy in solid tumors.…”