100 258

Cited 5 times in

TUSC2 immunogene enhances efficacy of chemo-immuno combination on KRAS/LKB1 mutant NSCLC in humanized mouse model

Authors
 Ismail M Meraz  ;  Mourad Majidi  ;  RuPing Shao  ;  Feng Meng  ;  Min Jin Ha  ;  Elizabeth Shpall  ;  Jack A Roth 
Citation
 COMMUNICATIONS BIOLOGY, Vol.5(1) : 167, 2022-02 
Journal Title
COMMUNICATIONS BIOLOGY
Issue Date
2022-02
MeSH
AMP-Activated Protein Kinases* / genetics ; AMP-Activated Protein Kinases* / immunology ; Animals ; Antibodies, Monoclonal, Humanized / administration & dosage ; Antineoplastic Combined Chemotherapy Protocols / pharmacology* ; Carboplatin / administration & dosage ; Carcinoma, Non-Small-Cell Lung* / drug therapy ; Carcinoma, Non-Small-Cell Lung* / genetics ; Carcinoma, Non-Small-Cell Lung* / therapy ; Disease Models, Animal ; Genes, Tumor Suppressor ; Lung Neoplasms* / drug therapy ; Lung Neoplasms* / genetics ; Lung Neoplasms* / therapy ; Mice ; Proto-Oncogene Proteins p21(ras)* / genetics ; Proto-Oncogene Proteins p21(ras)* / immunology ; Tumor Microenvironment ; Tumor Suppressor Proteins* / genetics ; Tumor Suppressor Proteins* / immunology
Abstract
KRAS/LKB1 (STK11) NSCLC metastatic tumors are intrinsically resistant to anti-PD-1 or PD-L1 immunotherapy. In this study, we use a humanized mouse model to show that while carboplatin plus pembrolizumab reduce tumor growth moderately and transiently, the addition of the tumor suppressor gene TUSC2, delivered systemically in nanovesicles, to this combination, eradicates tumors in the majority of animals. Immunoprofiling of the tumor microenvironment shows the addition of TUSC2 mediates: (a) significant infiltration of reconstituted human functional cytotoxic T cells, natural killer cells, and dendritic cells; (b) induction of antigen-specific T cell responses; (c) enrichment of functional central and memory effector T cells; and (d) decreased levels of PD-1+ T cells, myeloid-derived suppressor cells, Tregs, and M2 tumor associated macrophages. Depletion studies show the presence of functional central and memory effector T cells are required for the efficacy. TUSC2 sensitizes KRAS/LKB1 tumors to carboplatin plus pembrolizumab through modulation of the immune contexture towards a pro-immune tumor microenvironment.
Files in This Item:
T202202164.pdf Download
DOI
10.1038/s42003-022-03103-7
Appears in Collections:
4. Graduate School of Public Health (보건대학원) > Graduate School of Public Health (보건대학원) > 1. Journal Papers
Yonsei Authors
Ha, Min Jin(하민진)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/189285
사서에게 알리기
  feedback

qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse

Links