# Immunotherapies for Ischemic Stroke Patients: Current Status and Future Directions

**Authors:** Riley M. McCabe, Lauren Hurley, Kasey Pull, Nafisa M. Jadavji

PMC · DOI: 10.3390/medsci14010111 · 2026-02-25

## TL;DR

This review explores how targeting the immune system could improve outcomes for ischemic stroke patients by reducing neuroinflammation and tailoring treatments to individual needs.

## Contribution

The paper provides a comprehensive review of immune system targeting in ischemic stroke and emphasizes the importance of sex-specific interventions.

## Key findings

- Reducing neuroinflammation is crucial for minimizing brain tissue loss and functional impairments after stroke.
- Combination therapies, including immune-based treatments and personalized pharmaceuticals, may improve patient outcomes.
- Sex differences in stroke outcomes suggest the need for sex-specific treatment strategies.

## Abstract

Background/Objectives: Ischemic stroke occurs when a thrombus forms within a blood vessel in the brain. This results in reduced levels of oxygen and glucose, leading to the death of cells and a reduction in function. There are several molecular signaling cascades that commence after the onset of an ischemic stroke; these include increases in apoptosis, oxidative stress, neuroinflammation, as well as others. The aim of this review is to provide an updated synthesis of the impact ischemic stroke has on the immune system and how the immune system can be targeted to improve outcomes post-stroke. Methods: In this review, we have included both clinical and pre-clinical studies and provide a discussion for future directions given our synthesis of the data. Results: It is evident that reducing neuroinflammation is an important component of reducing brain tissue loss and functional impairments after stroke. A combination of therapies may be more effective for stroke-affected patients. This could include reducing neuroinflammation through immune therapies, in combination with some pharmaceuticals specific to the patient’s needs. Furthermore, sex differences are highly prevalent in ischemic stroke outcomes. These differences can inform us of the best sex-specific interventions, treatments, or techniques that should be used in healthcare to ensure lower mortality rates and higher quality of life for all. Therapeutic development for ischemic stroke is needed, and this review highlights that targeting the immune system could lead to better outcomes for patients.

## Linked entities

- **Diseases:** ischemic stroke (MONDO:1060198)

## Full-text entities

- **Genes:** Plat (plasminogen activator, tissue) [NCBI Gene 18791] {aka D8Ertd2e, tPA}, Nt5c (5',3'-nucleotidase, cytosolic) [NCBI Gene 50773] {aka Dnt, Dnt1, Umph-2, Umph2}, Mtor (mechanistic target of rapamycin kinase) [NCBI Gene 56717] {aka 2610315D21Rik, FRAP, FRAP2, Frap1, RAFT1, RAPT1}, Il1rn (interleukin 1 receptor antagonist) [NCBI Gene 16181] {aka F630041P17Rik, IL-1ra}, Trav6-3 (T cell receptor alpha variable 6-3) [NCBI Gene 328483] {aka Gm13948, Gm193, Gm4, TCR}, Igha (immunoglobulin heavy constant alpha) [NCBI Gene 238447] {aka IgA, Igh-2}, Cmtm2a (CKLF-like MARVEL transmembrane domain containing 2A) [NCBI Gene 73381] {aka 1700001K04Rik, 1700041N15Rik, 1700063K20Rik, ARR19, C32, CKLF3}, Ccr2 (C-C motif chemokine receptor 2) [NCBI Gene 12772] {aka Cc-ckr-2, Ccr2a, Ccr2b, Ckr2, Ckr2a, Ckr2b}, Icam1 (intercellular adhesion molecule 1) [NCBI Gene 15894] {aka CD54, Icam-1, Ly-47, MALA-2}, Il10 (interleukin 10) [NCBI Gene 16153] {aka CSIF, If2a, Il-10}, Tlr4 (toll-like receptor 4) [NCBI Gene 29260], ADAMTS13 (ADAM metallopeptidase with thrombospondin type 1 motif 13) [NCBI Gene 11093] {aka ADAM-TS13, ADAMTS-13, C9orf8, VWFCP, vWF-CP}, Inhba (inhibin subunit beta A) [NCBI Gene 29200], IL1B (interleukin 1 beta) [NCBI Gene 3553] {aka IL-1, IL1-BETA, IL1F2, IL1beta}, Tlr4 (toll-like receptor 4) [NCBI Gene 21898] {aka Lps, Ly87, Ran/M1, Rasl2-8}, Vegfa (vascular endothelial growth factor A) [NCBI Gene 22339] {aka L-VEGF, Vegf, Vpf}, PPARA (peroxisome proliferator activated receptor alpha) [NCBI Gene 5465] {aka NR1C1, PPAR, PPAR-alpha, PPARalpha, hPPAR}, PLAT (plasminogen activator, tissue type) [NCBI Gene 5327] {aka T-PA, TPA}, Parp1 (poly (ADP-ribose) polymerase family, member 1) [NCBI Gene 11545] {aka 5830444G22Rik, ARTD1, Adprp, Adprt1, PARP, PPOL}, Il13 (interleukin 13) [NCBI Gene 16163] {aka Il-13}, Ly96 (lymphocyte antigen 96) [NCBI Gene 17087] {aka ESOP-1, MD-2, MD2}, Igh-V7183 (immunoglobulin heavy chain (V7183 family)) [NCBI Gene 16059] {aka B9-scFv, IgG, IgH, IgVH1(VSG), VH7183, VI24H}, CREB1 (cAMP responsive element binding protein 1) [NCBI Gene 1385] {aka CREB, CREB-1}, FASLG (Fas ligand) [NCBI Gene 356] {aka ALPS1B, APT1LG1, APTL, CD178, CD95-L, CD95L}, COX2 (cytochrome c oxidase subunit II) [NCBI Gene 17709], Il4 (interleukin 4) [NCBI Gene 16189] {aka BSF-1, Il-4}, Fasl (Fas ligand) [NCBI Gene 14103] {aka APT1LG1, CD178, CD95-L, CD95L, Fas-L, Faslg}, Traf6 (TNF receptor-associated factor 6) [NCBI Gene 22034] {aka 2310003F17Rik, C630032O20Rik}, Casp3 (caspase 3) [NCBI Gene 12367] {aka A830040C14Rik, AC-3, CASP-3, CC3, CPP-32, CPP32}, IFNG (interferon gamma) [NCBI Gene 3458] {aka IFG, IFI, IMD69}, Trem2 (triggering receptor expressed on myeloid cells 2) [NCBI Gene 301227] {aka Trem2-Mia, Trem2-Mib}, HMGB1 (high mobility group box 1) [NCBI Gene 3146] {aka HMG-1, HMG1, HMG3, SBP-1}, Gfap (glial fibrillary acidic protein) [NCBI Gene 14580], Mag (myelin-associated glycoprotein) [NCBI Gene 29409] {aka 1B236}, Nfkb1 (nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105) [NCBI Gene 18033] {aka NF-KB1, NF-kappaB, NF-kappaB1, p105, p50, p50/p105}, CRP (C-reactive protein) [NCBI Gene 1401] {aka PTX1}, CASP1 (caspase 1) [NCBI Gene 834] {aka ICE, IL1BC, P45}, Cd86 (CD86 antigen) [NCBI Gene 12524] {aka B7, B7-2, B7.2, B70, CLS1, Cd28l2}, NR3C1 (nuclear receptor subfamily 3 group C member 1) [NCBI Gene 2908] {aka GCCR, GCR, GCRST, GR, GRL}, TREM1 (triggering receptor expressed on myeloid cells 1) [NCBI Gene 54210] {aka CD354, TREM-1}, Mrc1 (mannose receptor, C type 1) [NCBI Gene 17533] {aka CD206, MR}, Pdcd1lg2 (programmed cell death 1 ligand 2) [NCBI Gene 58205] {aka B7-DC, Btdc, F730015O22Rik, PD-L2}, REN (renin) [NCBI Gene 5972] {aka ADTKD4, HNFJ2, RTD}, VWF (von Willebrand factor) [NCBI Gene 7450] {aka F8VWF, VWD}, Cxcr3 (C-X-C motif chemokine receptor 3) [NCBI Gene 12766] {aka Cd183, Cmkar3}, Trem2 (triggering receptor expressed on myeloid cells 2) [NCBI Gene 83433] {aka TREM-2, Trem2a, Trem2b, Trem2c}, Edn1 (endothelin 1) [NCBI Gene 13614] {aka ET-1, PPET1, preproET}, Il1 (interleukin 1 complex) [NCBI Gene 111343] {aka Il-1}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, Cxcl10 (C-X-C motif chemokine ligand 10) [NCBI Gene 15945] {aka C7, CRG-2, INP10, IP-10, IP10, Ifi10}, Ptgs2 (prostaglandin-endoperoxide synthase 2) [NCBI Gene 19225] {aka COX2, Cox-2, PES-2, PGHS-2, PHS II, PHS-2}, Il2rb (interleukin 2 receptor, beta chain) [NCBI Gene 16185] {aka CD122, IL-15Rbeta, IL15Rbeta, Il-2/15Rbeta, Il-2Rbeta, p70}, Tnf (tumor necrosis factor) [NCBI Gene 21926] {aka DIF, TNF-a, TNF-alpha, TNFSF2, TNFalpha, Tnfa}, Rag1 (recombination activating 1) [NCBI Gene 19373] {aka Rag-1}, MAG (myelin associated glycoprotein) [NCBI Gene 4099] {aka GMA, S-MAG, SIGLEC-4A, SIGLEC4, SIGLEC4A, SPG75}, RXRA (retinoid X receptor alpha) [NCBI Gene 6256] {aka NR2B1, RXR-alpha, RXRalpha}, Casp1 (caspase 1) [NCBI Gene 12362] {aka ICE, Il1bc}, Cd274 (CD274 antigen) [NCBI Gene 60533] {aka A530045L16Rik, B7h1, Pdcd1l1, Pdcd1lg1, Pdl1}, Il17f (interleukin 17F) [NCBI Gene 257630] {aka IL-17F}
- **Diseases:** AIS (MESH:D000083242), thrombus (MESH:D013927), Inflammation (MESH:D007249), neuron loss (MESH:D009410), Coma (MESH:D003128), ischemic damage (MESH:D017202), brain damage (MESH:D001925), hypoxic (MESH:D002534), neurological deficit (MESH:D009461), hypertension (MESH:D006973), NIHSS (MESH:C538175), tissue damage (MESH:D017695), hypoxia (MESH:D000860), brain tissue loss (MESH:D001927), spleen damage (MESH:D013160), induced immunodepression syndrome (MESH:D000092582), antiphospholipid syndrome (MESH:D016736), post-stroke dementia (MESH:D003704), ischemic (MESH:D002545), occlusions (MESH:D001157), gait impairment (MESH:D020234), neurodegeneration (MESH:D019636), mitochondrial dysfunction (MESH:D028361), ischemia (MESH:D007511), myelin damage (MESH:D020279), Neuroinflammation (MESH:D000090862), locomotor deficits (MESH:D001523), toxicity (MESH:D064420), bacterial infection (MESH:D001424), death (MESH:D003643), infarct (MESH:D007238), brain injury (MESH:D001930), cerebral hemorrhagic transformation (MESH:D002543), injury to (MESH:D014947), Ischemic Stroke (MESH:D002544), cardioembolic stroke (MESH:D000083262), infections (MESH:D007239), Post-stroke (MESH:D020521), ACS (MESH:D020520), MCAO (MESH:D020244)
- **Chemicals:** glucose (MESH:D005947), fluorescein (MESH:D019793), water (MESH:D014867), LPS (MESH:D008070), tetracycline (MESH:D013752), PGE2 (MESH:D015232), choline (MESH:D002794), aspirin (MESH:D001241), Cornuside (MESH:C080726), Minocycline (MESH:D008911), STS (MESH:C024894), ROS (MESH:D017382), salvianic acid A (MESH:C035055), Fingolimod (MESH:D000068876), Natalizumab (MESH:D000069442), iron (MESH:D007501), CSO (MESH:D003369), INCB 3344 (MESH:C505875), GSK249320 (MESH:C581856), oxygen (MESH:D010100), IL-37 (-), nitric oxide (MESH:D009569)
- **Species:** Rattus norvegicus (brown rat, species) [taxon 10116], Adeno-associated virus (species) [taxon 272636], Homo sapiens (human, species) [taxon 9606], Mus musculus (house mouse, species) [taxon 10090]
- **Cell lines:** RAW264.7 — Mus musculus (Mouse), Mouse leukemia, Cancer cell line (CVCL_0493)

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Source: https://tomesphere.com/paper/PMC13027835