The helminth-derived peptide GK-1 induces an anti-tumoral CD8 T cell response associated with downregulation of the PD-1/PD-L1 pathway

Rodríguez-Rodríguez, Noé; Madera-Salcedo, Iris K.; Bugarin-Estrada, Emmanuel; Sánchez-Miranda, Elizabeth; Torres-García, Diana; Cervantes‐Torres, Jacquelynne; Fragoso, Gladis; Rosetti, Florencia; Crispín, José C.; Sciutto, Edda

doi:10.1016/j.clim.2019.07.006

Cited by 7 publications

(4 citation statements)

References 14 publications

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“…(b) Some tapeworm products could boost various (innate or adaptive) components of the immune system, which could then eliminate the cancer cells. The most probable mechanism is the activation of tumor-infiltrating NK cells or specific anti-tumor CD8+ T cells ( Rodríguez-Rodríguez et al, 2020 ; Berriel et al, 2021 ). (c) It seems that some parasite-derived molecules directly affect cancer cells (their activities, including replication, migration, invasiveness, apoptosis, etc .…”

Section: Discussionmentioning

confidence: 99%

“…There was also an increase in the population of tumor-infiltrating CD8+ T cells, with decreased PD1 (receptor for PDL1) expression in these CD8+ T cells. Reducing PD1 expression in activated lymphocytes could increase their cytotoxic activity and lead to the observed suppression of tumor growth ( Rodríguez-Rodríguez et al, 2020 ).…”

Section: Survey Methodologymentioning

confidence: 99%

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How tapeworms interact with cancers: a mini-review

Schreiber,

Vajs,

Horák

2024

PeerJ

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Cancer is one of the leading causes of death, with an estimated 19.3 million new cases and 10 million deaths worldwide in 2020 alone. Approximately 2.2 million cancer cases are attributed to infectious diseases, according to the World Health Organization (WHO). Despite the apparent involvement of some parasitic helminths (especially trematodes) in cancer induction, there are also records of the potential suppressive effects of helminth infections on cancer. Tapeworms such as Echinococcus granulosus, Taenia crassiceps, and more seem to have the potential to suppress malignant cell development, although in a few cases the evidence might be contradictory. Our review aims to summarize known epidemiological data on the cancer-helminth co-occurrence in the human population and the interactions of tapeworms with cancers, i.e., proven or hypothetical effects of tapeworms and their products on cancer cells in vivo (i.e., in experimental animals) or in vitro. The prospect of bioactive tapeworm molecules helping reduce the growth and metastasis of cancer is within the realm of future possibility, although extensive research is yet required due to certain concerns.

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Section: Discussionmentioning

confidence: 99%

Section: Survey Methodologymentioning

confidence: 99%

How tapeworms interact with cancers: a mini-review

Schreiber,

Vajs,

Horák

2024

PeerJ

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“…A combination of PD-L1 immunotherapy with other drugs can bring in better results. For instance, a combination of GK-1, a peptide derived from helminth Taenia Crassiceps, with an anti-PD-L1 therapy can increase survival time and enhance T cell function in mice models [89,90] . PV-10, a 10% solution of rose bengal disodium, is another chemical that has synergistic effects when used with an anti-PD-L1 antibody.…”

Section: Melanomamentioning

confidence: 99%

The role of PD-1/PD-L1 signaling pathway in cancer pathogenesis and treatment: a systematic review

Sabaghian,

Shamsabadi,

Momeni

et al. 2024

J Cancer Metastasis Treat

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Aim: Cancer as a complex disease poses significant challenges for both diagnosis and treatment. Researchers have been exploring various avenues to find effective therapeutic strategies, with a particular emphasis on cellular signaling pathways and immunotherapy. One such pathway that has recently been suggested is the PD-1/PD-L1 pathway, which is an immune checkpoint signaling system that plays an important role in regulating the immune system and maintaining tissue homeostasis. Cancer cells exploit this pathway by producing PD-L1, which attaches to PD-1 on T cells, thus inhibiting immune responses and enabling the cancer cells to escape detection by the immune system. This study aimed to evaluate the role of the PD-1/PD-L1 pathway in cancer pathogenesis and treatment. Method: This study was performed based on the principles of Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA). All in vitro , in vivo , and clinical studies that were published in English have been considered during a thorough search of the Scopus, Web of Science, and PubMed databases without date restriction until March 2024. Results: According to the studies reviewed, the PD-1/PD-L1 signaling axis suggests promising therapeutic effects on various types of cancers such as non-small cell lung cancer, melanoma, breast cancer, hepatocellular carcinoma, squamous cell carcinoma, and colorectal cancer, among others. Additionally, research suggests that immune checkpoint inhibitors that block PD1/PD-L1, such as pembrolizumab, atezolizumab, nivolumab, durvalumab, cemiplimab, avelumab, etc. , can effectively prevent tumor cells from escaping the immune system. Moreover, there might be a possible interaction between microbiome, obesity, etc. on immune mechanisms and on the immune checkpoint inhibitors (ICIs). Conclusion: Although we have gained considerable knowledge about ICIs, we are still facing challenges in effectively prescribing the appropriate ICIs for individual patients. This is largely due to the complex interactions between different intracellular pathways, which need to be thoroughly studied. To resolve this issue, it is necessary to conduct more reliable clinical trials that can produce a scientific consensus.

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“…Moreover, PD-L1 is associated with CD8 T-cell-enriched immune environments and specific gene expression characteristics, as well as type-1 T-helper-cell cytokine, chemokine, and interferon production . In cancer cells, PD-L1, as a protumor factor, activates proliferative- and survival-signaling pathways by binding to its receptor, , indicating the association of PD-L1 with tumor progression . Moreover, PD-L1 exerts a nonimmune proliferative effect on various types of tumor cells .…”

Section: Introductionmentioning

confidence: 99%

Structure-Guided Discovery of PD-1/PD-L1 Interaction Inhibitors: Peptide Design, Screening, and Optimization via Computation-Aided Phage Display Engineering

Tseng,

Lee,

Chen

et al. 2024

J. Chem. Inf. Model.

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Cancer immunotherapy harnesses the immune system to combat tumors and has emerged as a major cancer treatment modality. The PD-1/PD-L1 immune checkpoint modulates interactions between tumor cells and T cells and has been extensively targeted in cancer immunotherapy. However, the monoclonal antibodies known to target this immune checkpoint have considerable side effects, and novel PD-1/PD-L1 inhibitors are therefore required. Herein, a peptide inhibitor to disrupt PD-1/ PD-L1 interactions was designed through structure-driven phage display engineering coupled to computational modification and optimization. BetaPb, a novel peptide library constructed by using the known structure of PD-1/PD-L, was used to develop inhibitors against the immune checkpoint, and specific peptides with high affinity toward PD-1 were screened through enzyme-linked immunosorbent assays, homogeneous time-resolved fluorescence, and biolayer interferometry. A potential inhibitor, B8, was preliminarily screened through biopanning. The binding affinity of B8 toward PD-1 was confirmed through computation-aided optimization. Assessment of B8 variants (B8.1, B8.2, B8.3, B8.4, and B8.5) demonstrated their attenuation of PD-1/PD-L1 interactions. B8.4 exhibited the strongest attenuation efficiency at a half-maximal effective concentration of 0.1 μM and the strongest binding affinity to PD-1 (equilibrium dissociation constant = 0.1 μM). B8.4 outperformed the known PD-1/PD-L1 interaction inhibitor PL120131 in disrupting PD-1/PD-L1 interactions, revealing that B8.4 has remarkable potential for modification to yield an antitumor agent. This study provides valuable information for the future development of peptide-based drugs, therapeutics, and immunotherapies for cancer.

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The helminth-derived peptide GK-1 induces an anti-tumoral CD8 T cell response associated with downregulation of the PD-1/PD-L1 pathway

Cited by 7 publications

References 14 publications

How tapeworms interact with cancers: a mini-review

How tapeworms interact with cancers: a mini-review

The role of PD-1/PD-L1 signaling pathway in cancer pathogenesis and treatment: a systematic review

Structure-Guided Discovery of PD-1/PD-L1 Interaction Inhibitors: Peptide Design, Screening, and Optimization via Computation-Aided Phage Display Engineering

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