LCP2 mediates SUV39H1-driven cellular senescence-related chemoresistance in natural killer/T-cell lymphoma.

Zhang Y, Qian S, Yang Q, Shi Z, Dong M, Wang Z, Yang Z, Wu S, Li Z, Zhang M, Zhang X, Chen Q

Cell death & disease28 May 2026

PMID42209466PMCIDPMC13408427DOI10.1038/s41419-026-08897-6PepBankPUB-42209466

Summary

Natural killer/T-cell lymphoma (NKTCL) is an aggressive haematological malignancy with poor prognosis, particularly in patients with relapsed/refractory (R/R) disease. The mechanisms underlying multidrug resistance in NKTCL remain unclear and present an urgent challenge that must be addressed during clinical treatment. Multidrug-resistant NKTCL models were established using adriamycin (ADM), and cellular senescence was confirmed by markers including P16, P21, and senescence-associated β-galactosidase (SA-β-gal). Proteomic sequencing of plasma from clinical patients and resistant cells identified LCP2 as a key protein. Phosphoproteomics, mass spectrometry, and co-immunoprecipitation analyses revealed LCP2's role in mediating senescence-associated chemoresistance. An in vivo ageing microenvironment model was used to assess whether targeting the LCP2-mediated axis could eliminate chemoresistant senescent cells. Results show that ADM-resistant NKTCL cells exhibited phenotypic and senescence features. Of these, LCP2 expression was significantly reduced in the plasma of R/R NKTCL patients and in chemoresistant cells, correlating inversely with senescence marker SA-β-gal. Moreover, LCP2 knockdown enhanced the chemoresistance, senescent-associated secretory phenotype secretion, and G0/G1 cell cycle arrest in NKTCL cells. Mechanistically, LCP2 deficiency activated the IQGAP2/LaminA/C/SUV39H1 axis, thus driving DNA damage, telomere stress-induced senescence, and facilitating the formation of an immunosuppressive microenvironment. Importantly, targeting this axis with Epitalon and Chaetocin can partially eliminate therapy-induced senescent cells, enhance response to chemotherapeutics, and alleviate the immunosuppressive microenvironment to a certain extent in vivo. In conclusion, this study is the first to uncover LCP2 as a critical biomarker of senescence-related chemoresistance in NKTCL, providing a theoretical basis for the clinical translation of senolytics for treating R/R NKTCL.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study3

No result from this study comes from a test of the peptide.

Studies that did not test the peptide alone3

In this study, Epitalon was a lab tool or a carrier, part of a mix, or the subject of a lab method. These results are not evidence about taking Epitalon.

01AnimalNot a test of Epitalon aloneAnimal study (in vivo)Efficacy outcome
In an in vivo ageing microenvironment model of NK/T-cell lymphoma, targeting the LCP2-mediated axis with Epitalon plus Chaetocin partially eliminated therapy-induced senescent cells.
In plain wordsIn an animal model of lymphoma, Epitalon combined with chaetocin partly cleared aged cancer-treatment-resistant cells.
Peptide
Epitalon
Outcome
DecreaseTherapy-induced senescent cells
Study
n: not reported in source
In vivo ageing microenvironment model
Outcome group
Aging markers · Cancer
Source sentences
Summary
Importantly, targeting this axis with Epitalon and Chaetocin can partially eliminate therapy-induced senescent cells
1 context sentence(design, population, supporting numbers)
Summary · context
An in vivo ageing microenvironment model was used to assess whether targeting the LCP2-mediated axis could eliminate chemoresistant senescent cells.
In this study, Epitalon was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Epitalon.
Show in the study text Report a problemFND-4220946601
02AnimalNot a test of Epitalon aloneAnimal study (in vivo)Efficacy outcome
In an in vivo ageing microenvironment model of NK/T-cell lymphoma, Epitalon plus Chaetocin enhanced the response to chemotherapeutics.
In plain wordsIn an animal model of lymphoma, Epitalon combined with chaetocin improved the response to chemotherapy.
Peptide
Epitalon
Outcome
IncreaseResponse to chemotherapeutics
Study
n: not reported in source
In vivo ageing microenvironment model
Outcome group
Tumor growth · Cancer
Source sentences
Summary
Importantly, targeting this axis with Epitalon and Chaetocin
2 context sentences(design, population, supporting numbers)
Summary · context
enhance response to chemotherapeutics
Summary · context
An in vivo ageing microenvironment model was used to assess whether targeting the LCP2-mediated axis could eliminate chemoresistant senescent cells.
In this study, Epitalon was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Epitalon.
Show in the study text Report a problemFND-4220946602
03AnimalNot a test of Epitalon aloneAnimal study (in vivo)Efficacy outcome
In an in vivo ageing microenvironment model of NK/T-cell lymphoma, Epitalon plus Chaetocin alleviated the immunosuppressive microenvironment to a certain extent.
In plain wordsIn an animal model of lymphoma, Epitalon combined with chaetocin eased the immune-suppressing tumor surroundings to some extent.
Peptide
Epitalon
Outcome
DecreaseImmunosuppressive microenvironment
Study
n: not reported in source
In vivo ageing microenvironment model
Outcome group
Immune response · Cancer
Source sentences
Summary
alleviate the immunosuppressive microenvironment to a certain extent in vivo
1 context sentence(design, population, supporting numbers)
Summary · context
An in vivo ageing microenvironment model was used to assess whether targeting the LCP2-mediated axis could eliminate chemoresistant senescent cells.
In this study, Epitalon was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Epitalon.
Show in the study text Report a problemFND-4220946603

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
10 Oct 2026, 08:19 UTC
Study results updated
Version 1
9 Oct 2026, 02:47 UTC
First added · source update from Europe PMC

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