Comprehensive transcriptome profiling in elderly cancer patients reveals aging-altered immune cells and immune checkpoints.

Aging is the single most significant risk factor for cancer development. However, the potential impact of aging on cancer microenvironment remains poorly understood. Here, we performed a pan-cancer transcriptome analysis to identify aging-specific molecular patterns across 18 cancer types. Strikingly, aging-specific molecular features define human cancers into two types, including the strong and weak aging-effect groups. Significant aging associated molecular signature was observed in 16 cancer types (strong aging-effect group) such as breast invasive carcinoma and acute myeloid leukemia. In such 16 cancer types, old patients showed obvious poor survival compared to young patients, but this observation was not found in the weak aging-effect cancers. Aging-associated cancer-relevant molecules significantly enriched in 23 pathways including EMT and KRAS signaling. More interestingly, in cancer microenvironment, aging significantly restrains adaptive immunity, but strikingly, increases the number of infiltrated innate immune cells. Further analysis shows that the expression of immune checkpoints including PD-1, PD-L1, PD-L2 and CTLA-4 are mostly correlated with age. In general, cancer cells in elderly patients show a more aggressive phenotype and their surrounding microenvironment is under a more immune suppression status compared to young patients. Our study provides a systematic understanding of aging-associated molecular features in pan-cancer and indicates a clinical requirement to develop aging-specific therapeutic strategies in a majority of cancer types. Furthermore, aging-altered immune cells and immune checkpoints should be considered in cancer immunotherapy.