Examining the Relationship between Circulating CD4- CD8- Double-Negative T Cells and Outcomes of Immuno-Checkpoint Inhibitor Therapy-Looking for Biomarkers and Therapeutic Targets in Metastatic Melanoma.
Adult
Aged
Aged, 80 and over
Antibodies, Monoclonal
/ therapeutic use
Antineoplastic Agents
/ therapeutic use
Biomarkers
/ analysis
CD8-Positive T-Lymphocytes
/ immunology
Carcinoma, Non-Small-Cell Lung
/ drug therapy
Female
Humans
Immunotherapy
/ methods
Lung Neoplasms
/ drug therapy
Male
Melanoma
/ immunology
Middle Aged
checkpoint inhibitors
double negative T cells
immunotherapy resistance
melanoma
Journal
Cells
ISSN: 2073-4409
Titre abrégé: Cells
Pays: Switzerland
ID NLM: 101600052
Informations de publication
Date de publication:
16 02 2021
16 02 2021
Historique:
received:
31
12
2020
revised:
10
02
2021
accepted:
14
02
2021
entrez:
6
3
2021
pubmed:
7
3
2021
medline:
16
10
2021
Statut:
epublish
Résumé
The role of circulating CD4 We performed a basal and longitudinal assessment of circulating immune cells, including DNTs, in metastatic melanoma patients treated with checkpoint blockade in a single-center cohort, and examined the correlations levels of immune cells with clinical features and therapy outcomes. Sixty-eight patients (48 ipilimumab, 20 PD1 inhibitors) were enrolled in the study. Our analysis indicated that better outcomes were associated with normal LDH, fewer than three metastatic sites, an ECOG performance status of 0, M1a stage, lower WBC and a higher lymphocyte count. The increase in lymphocyte count and decrease of DNTs were significantly associated with the achievement of an overall response. The median value of DNT decreased while the CD4+ and NK cells increased in patients that responded to treatment compare to those who did not respond to treatment. DNT cells change during treatment with checkpoint inhibitors and may be adept at sensing the immune response to melanoma. The complementary variation of DNT cells with respect to CD4+ and other immune actors may improve the reliability of lymphocyte assessment. Further investigation of DNT as a potential target in checkpoint inhibitor resistant melanoma is warranted.
Sections du résumé
BACKGROUND
The role of circulating CD4
METHODS
We performed a basal and longitudinal assessment of circulating immune cells, including DNTs, in metastatic melanoma patients treated with checkpoint blockade in a single-center cohort, and examined the correlations levels of immune cells with clinical features and therapy outcomes.
RESULTS
Sixty-eight patients (48 ipilimumab, 20 PD1 inhibitors) were enrolled in the study. Our analysis indicated that better outcomes were associated with normal LDH, fewer than three metastatic sites, an ECOG performance status of 0, M1a stage, lower WBC and a higher lymphocyte count. The increase in lymphocyte count and decrease of DNTs were significantly associated with the achievement of an overall response. The median value of DNT decreased while the CD4+ and NK cells increased in patients that responded to treatment compare to those who did not respond to treatment.
CONCLUSIONS
DNT cells change during treatment with checkpoint inhibitors and may be adept at sensing the immune response to melanoma. The complementary variation of DNT cells with respect to CD4+ and other immune actors may improve the reliability of lymphocyte assessment. Further investigation of DNT as a potential target in checkpoint inhibitor resistant melanoma is warranted.
Identifiants
pubmed: 33669266
pii: cells10020406
doi: 10.3390/cells10020406
pmc: PMC7920027
pii:
doi:
Substances chimiques
Antibodies, Monoclonal
0
Antineoplastic Agents
0
Biomarkers
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Références
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