Evidence map›Paper›PMID 41044622›Full record

ReviewCancer cell international2025

GRP-based vaccines as a novel approach in cancer immunotherapy: mechanisms, challenges, and prospects.

Razieh Malekian Shahreza, Hamed Zare, Nima Rastegar-Pouyani, Hamid Aria, Fatemeh Hakim, Mohammad Arefnia, Hamid Bakherad

Abstract readReview
In one paragraph

Review in Cancer cell international, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors.

Razieh Malekian Shahreza *Department of Pharmaceutical Biotechnology, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran.
Hamed Zare *Recombinant Proteins Department, Breast Cancer Research Center, Motamed Cancer Institute, ACECR, Tehran, Iran.
Nima Rastegar-PouyaniRecombinant Proteins Department, Breast Cancer Research Center, Motamed Cancer Institute, ACECR, Tehran, Iran.
Hamid AriaDepartment of Immunology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.
Fatemeh HakimDepartment of Biological Sciences, Institute for Advanced Studies in Basic Sciences (IASBS), Zanjan, Iran.
Mohammad ArefniaCell and molecular division, Biological science faculty, University of Isfahan, Isfahan, Iran.
Hamid BakheradDepartment of Pharmaceutical Biotechnology, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran. Bakheradh@pharm.mui.ac.ir.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Glucose-regulated proteins (GRPs), key members of the heat shock protein (HSP) family, function as molecular chaperones that are upregulated under endoplasmic reticulum (ER) stress. Prominent GRPs such as GRP78, GRP94/gp96, GRP75, and GRP170 play a great role in cancer cell survival and progression by promoting protein folding, immune evasion, and resistance to therapy. Within the tumor microenvironment, which is characterized by hypoxia, acidosis, and nutrient deprivation, GRPs can facilitate critical processes including proliferation, angiogenesis, metastasis, and apoptotic resistance. Moreover, beyond their intracellular roles, GRPs have been found to possess considerable immunogenic potential when expressed on the cell surface or secreted. As a result, these findings have led to the development of GRP-based cancer vaccines that can elicit robust adaptive immune responses by chaperoning tumor antigens to antigen-presenting cells. Current evidence suggests GRP75 (HSPA9/mortalin) is less immediately tractable than ER-resident GRPs (78/94/170) for vaccine design, primarily owing to its mitochondrial localization and poor antigen accessibility. However, nanoparticle-mediated delivery or CRISPR-engineered surface expression could reposition it as a future target, pending advances in intracellular antigen presentation pathways. Preclinical models have demonstrated that GRP-based immunotherapy can induce cytotoxic T lymphocyte responses and tumor regression. Additionally, repurposing GRP-targeted strategies from infectious, autoimmune, and neurodegenerative disease contexts may offer promising translational avenues in the field of cancer. Despite encouraging results, challenges such as tumor heterogeneity, immune suppression, and delivery optimization have still remained. Therefore, future research should aim to increase antigen specificity, optimize vaccine formulations, and explore combinatory regimens to overcome resistance mechanisms in cancer cells. Overall, GRP-targeted vaccines represent a very compelling candidate in cancer immunotherapy with great potentials for clinical translation in the future.

Indexed as

CancerChaperonER stressGRPsImmunotherapyVaccine

Identifiers

PMID41044622
PMCPMC12495762

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.