TY - JOUR
T1 - Efficacy of immune checkpoint inhibitors in upper tract urothelial carcinomas
T2 - Current knowledge and future directions
AU - Thouvenin, Jonathan
AU - Chanzá, Nieves Martínez
AU - Alhalabi, Omar
AU - Lang, Hervé
AU - Tannir, Nizar M.
AU - Barthélémy, Philippe
AU - Malouf, Gabriel G.
N1 - Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/9/1
Y1 - 2021/9/1
N2 - Upper tract urothelial carcinoma (UTUC) represents a rare and aggressive malignancy arising from the renal pelvis or ureter. It can develop sporadically or have a hereditary origin, such as Lynch syndrome, caused by DNA mismatch repair deficiency, leading to microsatellite instability phenotype. According to molecular characterization studies, UTUC presents different mutational profiles as compared to urinary bladder urothelial carcinomas. In particular, it has been reported that UTUC harbored a higher level of FGFR3 alterations associated with a T-cell depleted immune microenvironment. The therapeutic landscape in urothelial carcinoma is rapidly evolving, with immune checkpoint inhibitors forming part of the standard of care. A greater understanding of the molecular alterations and immune microenvironment leads to the development of new treatment combinations and targeted therapy. This review summarizes the available evidence concerning the use of immune checkpoint inhibitors and the biological rationale underlying their use in high-grade UTUC.
AB - Upper tract urothelial carcinoma (UTUC) represents a rare and aggressive malignancy arising from the renal pelvis or ureter. It can develop sporadically or have a hereditary origin, such as Lynch syndrome, caused by DNA mismatch repair deficiency, leading to microsatellite instability phenotype. According to molecular characterization studies, UTUC presents different mutational profiles as compared to urinary bladder urothelial carcinomas. In particular, it has been reported that UTUC harbored a higher level of FGFR3 alterations associated with a T-cell depleted immune microenvironment. The therapeutic landscape in urothelial carcinoma is rapidly evolving, with immune checkpoint inhibitors forming part of the standard of care. A greater understanding of the molecular alterations and immune microenvironment leads to the development of new treatment combinations and targeted therapy. This review summarizes the available evidence concerning the use of immune checkpoint inhibitors and the biological rationale underlying their use in high-grade UTUC.
KW - Epigenetic
KW - Genetic
KW - Immune checkpoint inhibitors
KW - Immunotherapy
KW - Upper tract urothelial carcinoma
KW - UTUC
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U2 - 10.3390/cancers13174341
DO - 10.3390/cancers13174341
M3 - Review article
C2 - 34503152
AN - SCOPUS:85113460429
SN - 2072-6694
VL - 13
JO - Cancers
JF - Cancers
IS - 17
M1 - 4341
ER -