TY - JOUR
T1 - Biomarkers for response to TIL therapy
T2 - a comprehensive review
AU - Albarrán Fernández, Víctor
AU - Ballestín Martínez, Pablo
AU - Stoltenborg Granhøj, Joachim
AU - Borch, Troels Holz
AU - Donia, Marco
AU - Marie Svane, Inge
N1 - © Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
PY - 2024/3/13
Y1 - 2024/3/13
N2 - Adoptive cell therapy with tumor-infiltrating lymphocytes (TIL) has demonstrated durable clinical responses in patients with metastatic melanoma, substantiated by recent positive results of the first phase III trial on TIL therapy. Being a demanding and logistically complex treatment, extensive preclinical and clinical effort is required to optimize patient selection by identifying predictive biomarkers of response. This review aims to comprehensively summarize the current evidence regarding the potential impact of tumor-related factors (such as mutational burden, neoantigen load, immune infiltration, status of oncogenic driver genes, and epigenetic modifications), patient characteristics (including disease burden and location, baseline cytokines and lactate dehydrogenase serum levels, human leucocyte antigen haplotype, or prior exposure to immune checkpoint inhibitors and other anticancer therapies), phenotypic features of the transferred T cells (mainly the total cell count, CD8:CD4 ratio, ex vivo culture time, expression of exhaustion markers, costimulatory signals, antitumor reactivity, and scope of target tumor-associated antigens), and other treatment-related factors (such as lymphodepleting chemotherapy and postinfusion administration of interleukin-2).
AB - Adoptive cell therapy with tumor-infiltrating lymphocytes (TIL) has demonstrated durable clinical responses in patients with metastatic melanoma, substantiated by recent positive results of the first phase III trial on TIL therapy. Being a demanding and logistically complex treatment, extensive preclinical and clinical effort is required to optimize patient selection by identifying predictive biomarkers of response. This review aims to comprehensively summarize the current evidence regarding the potential impact of tumor-related factors (such as mutational burden, neoantigen load, immune infiltration, status of oncogenic driver genes, and epigenetic modifications), patient characteristics (including disease burden and location, baseline cytokines and lactate dehydrogenase serum levels, human leucocyte antigen haplotype, or prior exposure to immune checkpoint inhibitors and other anticancer therapies), phenotypic features of the transferred T cells (mainly the total cell count, CD8:CD4 ratio, ex vivo culture time, expression of exhaustion markers, costimulatory signals, antitumor reactivity, and scope of target tumor-associated antigens), and other treatment-related factors (such as lymphodepleting chemotherapy and postinfusion administration of interleukin-2).
KW - Humans
KW - Lymphocytes, Tumor-Infiltrating
KW - Immunotherapy, Adoptive/methods
KW - Melanoma/drug therapy
KW - T-Lymphocytes/pathology
KW - Biomarkers/metabolism
UR - http://www.scopus.com/inward/record.url?scp=85187850284&partnerID=8YFLogxK
U2 - 10.1136/jitc-2023-008640
DO - 10.1136/jitc-2023-008640
M3 - Review
C2 - 38485186
SN - 2051-1426
VL - 12
JO - Journal for ImmunoTherapy of Cancer
JF - Journal for ImmunoTherapy of Cancer
IS - 3
M1 - e008640
ER -