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Emerging immune checkpoint targets and combination strategies in blood cancer immunotherapy

Mutaz Jamal Al-khreisatFaculty of Allied Medical Sciences, Hourani Center for Applied Scientific Research, Al-Ahliyya Amman University, Amman, JordanWaleed K. AbdulsahibDepartment of Pharmacology and Toxicology, College of Pharmacy, Al Farahidi University, Baghdad, Iraq. [email protected]Ihsan Khudhair JasimDepartment of Pharmaceutics, Faculty of Pharmacy, Al-Turath University, Baghdad, IraqH. MalathiDepartment of Biotechnology and Genetics, School of Sciences, JAIN (Deemed to be University), Bangalore, Karnataka, IndiaPradeepta Sekhar PatroDepartment of Immunology, IMS and SUM Hospital, Siksha 'O' Anusandhan, Bhubaneswar, 751003, Odisha, IndiaD. Alex AnandDepartment of Biomedical, Sathyabama Institute of Science and Technology, Chennai, Tamil Nadu, IndiaGunjan MukherjeeUniversity Institute of Biotechnology, Chandigarh University, Mohali, Punjab, IndiaAashna SinhaSchool of Applied and Life Sciences, Division of Research and Innovation, Uttaranchal University, Dehradun, Uttarakhand, IndiaDilnoz BuriyevaDepartment of Medicine, Termez University of Economics and Serviсe, Termez, Uzbekistan

Annals of Hematologyjournal2026en

ABI

Annotatsiya

Immunotherapy has revolutionized cancer treatment, offering durable responses across various malignancies. However, blood cancers present unique challenges due to significant heterogeneity, an immunosuppressive tumor microenvironment (TME), and potent mechanisms of immune evasion. This review synthesizes the current landscape of immune checkpoint blockade (ICB), evaluating both established agents and emerging targets (e.g., LAG-3, TIM-3, CD47) in hematologic malignancies. We critically examine the role of cancer stem cells (CSCs) in driving therapeutic resistance and recurrence, highlighting how aberrant signaling pathways (Wnt, Notch, m6A) fuel immune avoidance. Furthermore, we assess the transformative potential of cellular immunotherapies, specifically CAR-T and CAR-NK cells, proposing strategies to enhance their persistence and safety. By integrating insights from recent preclinical and clinical studies, this report provides a roadmap for developing rational, multi-pronged combination strategies that disrupt the “resistance ecosystem” of blood cancers, paving the way for personalized curative regimens.

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Mavzular

Cancer Immunotherapy and Biomarkers Immunotherapy and Immune Responses Immune cells in cancer

Identifikatorlar

DOI: 10.1007/s00277-026-06919-z

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