Quantifying the tumor microenvironment: what is the next step to advance cancer immunotherapy?

Recent breakthroughs in cancer immunotherapy have revolutionized cancer treatment. The focus of cancer treatment has shifted from tumor centric to tumor-host immune system interactions. Immune checkpoint inhibitors (CPI), particularly PD-1/PD-L1 inhibitors, have emerged as a new standard of care for multiple cancer types. However, only a fraction of patients (approximately 30–40%) respond to CPIs. [1]Sharma P, Hu-Lieskovan S, Wargo JA, Ribas A. Primary, adaptive, and acquired resistance to cancer immunotherapy. Cell 2017;168, 707–23.. Tumor intrinsic factors and the tumor microenvironment may contribute to response or resistance [1]Sharma P, Hu-Lieskovan S, Wargo JA, Ribas A. Primary, adaptive, and acquired resistance to cancer immunotherapy. Cell 2017;168, 707–23., [2]Kalbasi A, Ribas A. Tumour-intrinsic resistance to immune checkpoint blockade. Nat. Rev. Immunol. 2020; 25–39.. Thus, enormous efforts have been spent in profiling the tumor microenvironment (TME), including quickly accumulating single-cell RNA-seq datasets [3]Gohil SH, Iorgulescu JB, Braun DA, Keskin DB, Livak KJ. Applying high-dimensional single-cell technologies to the analysis of cancer immunotherapy. Nat. Rev. Clin. Oncol. 2021; 18, 244–56.. One of the central questions is how to identify the prognostic and predictive value of TME components, which could further guide patient treatment and potentially lead to discovery of new immune-oncology drug targets. Therefore, rapid progress is being made to understand the role of distinct components within the TME to modulate cancer progression [4]Ho WJ, Jaffee EM, Zheng L. The tumour microenvironment in pancreatic cancer—clinical challenges and opportunities. Nat. Rev. Clin. Oncol. 2020; 17, 527–40. This review will comment on the urgent need to quantify the TME to advance cancer immunotherapy.