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2017 ; 2
(12
): ä Nephropedia Template TP
gab.com Text
Twit Text FOAVip
Twit Text #
English Wikipedia
Mitochondrial dysregulation and glycolytic insufficiency functionally impair CD8
T cells infiltrating human renal cell carcinoma
#MMPMID28614802
Siska PJ
; Beckermann KE
; Mason FM
; Andrejeva G
; Greenplate AR
; Sendor AB
; Chiang YJ
; Corona AL
; Gemta LF
; Vincent BG
; Wang RC
; Kim B
; Hong J
; Chen CL
; Bullock TN
; Irish JM
; Rathmell WK
; Rathmell JC
JCI Insight
2017[Jun]; 2
(12
): ä PMID28614802
show ga
Cancer cells can inhibit effector T cells (Teff) through both immunomodulatory
receptors and the impact of cancer metabolism on the tumor microenvironment.
Indeed, Teff require high rates of glucose metabolism, and consumption of
essential nutrients or generation of waste products by tumor cells may impede
essential T cell metabolic pathways. Clear cell renal cell carcinoma (ccRCC) is
characterized by loss of the tumor suppressor von Hippel-Lindau (VHL) and altered
cancer cell metabolism. Here, we assessed how ccRCC influences the metabolism and
activation of primary patient ccRCC tumor infiltrating lymphocytes (TIL). CD8 TIL
were abundant in ccRCC, but they were phenotypically distinct and both
functionally and metabolically impaired. ccRCC CD8 TIL were unable to efficiently
uptake glucose or perform glycolysis and had small, fragmented mitochondria that
were hyperpolarized and generated large amounts of ROS. Elevated ROS was
associated with downregulated mitochondrial SOD2. CD8 T cells with hyperpolarized
mitochondria were also visible in the blood of ccRCC patients. Importantly,
provision of pyruvate to bypass glycolytic defects or scavengers to neutralize
mitochondrial ROS could partially restore TIL activation. Thus, strategies to
improve metabolic function of ccRCC CD8 TIL may promote the immune response to
ccRCC.
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