Immune and stromal scoring system associated with tumor microenvironment and prognosis: a gene-based multi-cancer analysis

Abstract

Abstract Background Tumor microenvironment (TME) is associated with tumor progression and prognosis. Previous studies provided tools to estimate immune and stromal cell infiltration in TME. However, there is still a lack of single index to reflect both immune and stromal status associated with prognosis and immunotherapy responses. Methods A novel immune and stromal scoring system named ISTMEscore was developed. A total of 15 datasets were used to train and validate this system, containing 2965 samples from lung adenocarcinoma, skin cutaneous melanoma and head and neck squamous cell carcinoma. Results The patients with high immune and low stromal scores (HL) were associated with low ratio of T cell co-inhibitory/stimulatory molecules and low levels of angiogenesis markers, while the patients with low immune and high stromal scores (LH) had the opposite characteristics. The HL patients had immune-centered networks, while the patients with low immune and low stromal scores (LL) had desert-like networks. Moreover, copy number alteration burden was decreased in the HL patients. For the clinical characteristics, our TME classification was an independent prognostic factor. In the 5 cohorts with immunotherapy, the LH patients were linked to the lowest response rate. Conclusions ISTMEscore system could reflect the TME status and predict the prognosis. Compared to previous TME scores, our ISTMEscore was superior in the prediction of prognosis and immunotherapy response.