Tumor microenvironment governs the prognostic landscape of immunotherapy for head and neck squamous cell carcinoma: A computational model-guided analysis
Fig 2
Explaining the phenotypic heterogeneity of the HNSCC TME.
(a) The nodes are either the cell states or the molecular species, whereas the edges represent diverse forms of interactions. The acronyms C_0, C_PDL1 + , and C_PDL1- refer to stem, PDL1+ (programed death ligand1), and PDL1- tumor cells, respectively. T_K + , T_K-, T_Help, T_Reg, and T_Ex stands for PD1+ (programmed death 1), PD1- killer T cells, Helper T cells, Regulatory T cells, and Exhausted T cells, respectively. M_1 and M_2 refer to macrophages of M1 and M2 phase, respectively. Further, F_WT and CAF correspond to wild-type and invasive cancer-associated fibroblasts, respectively. The acronyms IL-2, IL-8, IL-10 LIF, IFNG, IRF8, OPN, ICAM1, and Lac denote Interleukin-2, Interleukin-8, Interleukin-10, Leukemia Inhibitory Factor, Interferon Gamma, Interferon Regulatory Factor-8, Osteopontin, Intercellular Adhesion Molecule-1, and Lactate, respectively. Based on the accessibility of the tumor cells to the killer T cells, each of the three tumor cell states C_0, C + , and C- are further divided in to two categories Killer T-exposed and killer T non-exposed. S5 Text details all the abbreviations used in the network model. The killer T non-exposed tumor cell states are protected by the resident CAF population. (Refer to S1 Fig for detailed representation of the model) (b) We simulated the dynamics for 10,000 combinations of the parameters (that have a direct influence on the proliferation, conversion, and death of the CAF, Killer T, and tumor cells) based on the reconstructed network system to obtain the possible steady-state groups. We found five distinct groups: desert, immune desert, fibro desert, immune-dominated, and fibro-dominated. (c) The associated mapping of these five groups in the hyper-parameter space. (d-h) Bar charts for the median population of tumor cells, killer T cells, and CAF population across different groups.