ATM Gene Variations Predict Differences in Pretreatment Lung Inflammation in Non-Small Cell Lung Cancer (NSCLC) Patients

repopulation kinetics. Analyses utilized WT C57Bl/6 mice and B6.S129 p21-/mice. Results: We found that LCs do not undergo apoptosis following IR as do other DC subsets, but instead persist and migrate to skin-draining lymph nodes. Subsequent analysis in migration deficient CCR7-/mice revealed a constant number of epidermal LCs, indicating that changes in LC number following IR is due solely to migration and not to cell death. Further, the percentage of BrdU+ LCs doubles in the epidermis by day 7, contributing to full LC repopulation at day 14-post IR. Moreover, we show for the first time that LCs are resistant to the formation of DNA damage as measured by induction of H2AX foci and COMET assay. In contrast, other members of the myeloid lineage, notably lymphoid tissue-resident DCs, are exquisitely sensitive to IR-induced DNA damage. In addition, both steady state and post-lethal IR LCs express a unique repertoire of pro-survival and stress related proteins (Foxo3, p21, Bcl-xL, FGFR2) and diminished levels of pro-apoptotic molecules (Casp3, p53, Bim, Bid) by microarray analysis. Of interest, we found that LCs uniquely express p21 in the steady state myeloid compartment. Accordingly, we extended our analysis of the cellular effects of IR on LCs from p21-/-. We found that p21-/LCs had an impaired recovery following IR and were more radiosensitive. Conclusions: These data suggest that LCs uniquely express an IR-resistance module of genes that permit LCs to persist and repopulate the epidermal niche following IR. Future analyses will seek to elaborate the functional implications of LC and IR-sensitive DC IR-exposure as it relates to the priming and development of GVHD and local anti-tumor immunity following radiation therapy. Author Disclosure: J. Price: None. B. Hogstad: None. J. Idoyaga: None. M. LeBoeuf: None. C. Bigarella: None. S. Ghaffari: None. M.Merad: None.