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Arginase 2 is expressed by human lung cancer, but it neither induces immune suppression, nor affects disease
Rita Rotondo1, Luca Mastracci, Tiziana Piazza
1Department of Translational Oncology, National Institute for Cancer Research, Genoa, Italy.
Abstract:
In human prostate cancer, Arginase 2 (ARG2) and nitric oxide synthase (NOS) are concomitantly expressed by tumor cells, and induce tumor immune escape via peroxynitrite-dependent Tyrosine nitrosylation. Since there were no data regarding this immune suppressive mechanism in other tumor types, and an evaluation of its clinical relevance in human tumors had still to be provided, we have investigated presence and clinical relevance of ARG2 and NOS expression in lung cancer. No evidence of NOS expression was found, no significant NOS enzymatic activity was detected. Instead, ARG2 protein was expressed by tumor cells. In a cohort of 120 patients, the amount of ARG2-positive tumor cells was significantly higher in small cell lung cancers (SCLC) than in non-small cell lung cancers (NSCLC). Large cell undifferentiated carcinomas had twice ARG2 than the other NSCLC subtypes. ARG2 expression was increased in Grade 3 tumors, as compared to Grades 1 and 2. However, no relationship was found with tumor size and stage, and with patient survival. Indeed, the enzyme was active, since the Arginine catabolite Ornithine was produced, but Arginine depletion was not attained. In addition, nitrotyrosine was not found in tumor tissue. Accordingly, when tumor cells isolated from lung cancer were incubated with activated autologous T cells, no inhibition of proliferation was detected. Our results indicate that ARG2 is expressed in lung cancer, but it does not induce tumor immune escape and does not affect disease progression, most probably due to the lack of concomitant NOS expression.
Insights
Arginase 2 (ARG2) is present in lung cancer cells but does not suppress the immune system. Unlike prostate cancer, ARG2 in lung tumors does not drive immune escape or affect disease progression.
Area of Science:
- Oncology
- Immunology
- Biochemistry
Background:
- Arginase 2 (ARG2) and nitric oxide synthase (NOS) induce immune escape in prostate cancer via tyrosine nitrosylation.
- The role and clinical relevance of ARG2 and NOS in lung cancer immunity were previously uninvestigated.
Purpose of the Study:
- To investigate the presence and clinical relevance of ARG2 and NOS expression in lung cancer.
- To determine if ARG2-mediated immune suppression occurs in lung cancer.
Main Methods:
- Assessed ARG2 and NOS expression in lung tumor tissues from 120 patients.
- Measured ARG2 enzymatic activity and ornithine production.
- Evaluated nitrotyrosine presence and T cell proliferation inhibition in co-culture experiments.
Main Results:
- NOS expression and activity were not detected in lung cancer.
- ARG2 protein was expressed by tumor cells, with higher levels in small cell lung cancer (SCLC) and poorly differentiated tumors.
- ARG2 was enzymatically active, but arginine depletion, nitrotyrosine, and immune suppression were not observed.
Conclusions:
- ARG2 is expressed in lung cancer but does not induce immune escape or impact disease progression.
- The absence of concomitant NOS expression likely prevents the ARG2-mediated immune suppressive mechanism seen in prostate cancer.
