Loss-of-function alleles of P2RX7 and TLR4 fail to affect the response to chemotherapy in non-small cell lung cancer.
The success of anticancer chemotherapy relies at least in part on the induction of an immune response against tumor cells. Thus, tumors growing on mice that lack the pattern recognition receptor TLR4 or the purinergic receptor P2RX7 fail to respond to chemotherapy with anthracyclins or oxaliplatin in conditions in which the same neoplasms growing on immunocompetent mice would do so. Similarly, the therapeutic efficacy (measured as progression-free survival) of adjuvant chemotherapy with anthracyclins is reduced in breast cancer patients bearing loss-of-function alleles of TLR4 or P2RX7. TLR4 loss-of-function alleles also have a negative impact on the therapeutic outcome of oxaliplatin in colorectal cancer patients. Here, we report that loss-of-function TLR4 and P2RX7 alleles do not affect overall survival in non-small cell lung cancer (NSCLC) patients, irrespective of the administration and type of chemotherapy. The intrinsic characteristics of NSCLC (which near-to-always is chemoresistant and associated with poor prognosis) and/or the type of therapy that is employed to treat this malignancy (which near-to-always is based on cisplatin) may explain why two genes that affect the immune response to dying cells fail to influence the clinical progression of NSCLC patients.
INSERM; U848; Villejuif, France ; Institut Gustave Roussy; Villejuif, France ; Université Paris Sud-XI; Faculté de Médecine; Le Kremlin Bicêtre, France.
Erika
E
Vacchelli
Lorenzo
L
Galluzzi
Vanessa
V
Rousseau
Alice
A
Rigoni
Antoine
A
Tesniere
Nicolas
N
Delahaye
Fre de Ric
FD
Schlemmer
Laurie
L
Menger
Abdul Qader
AQ
Sukkurwala
Sandy
S
Adjemian
Isabelle
I
Martins
Mickaël
M
Michaud
Ariane
A
Dunant
Oliver
O
Kepp
Elisabeth
E
Brambilla
Jean-Charles
JC
Soria
Laurence
L
Zitvogel
Guido
G
Kroemer