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Tumor microenvironment governs the prognostic landscape of immunotherapy for head and neck squamous cell carcinoma: A computational model-guided analysis

Fig 5

Immune-dominated-- High immune accessibility, moderate CAF: For a given CAF-tumor interaction rate, lower T-cell cytotoxicity leads to higher PDL1^- to PDL1⁺ tumor cell population.

(a) For high levels of cytotoxicity, the tumor cell population remains insensitive to the proliferation rate () of the killer T cells in the immune dominated scenario. (b) CAF plays a dual role in governing the helper T cell population. CAF reduces the helper T cells via the regulatory T cells. However, a high tumor-promoting role of CAF increases the resident PDL1- -tumor cells that, in turn, increases the helper T cells via antigen sensing mechanism. (c) A high exhaustion rate can potentially increase the share of the PDL1- tumor cell population owing to the abundance of the exhausted tumor cells and their tumor-promoting effects. (d) The post-ICI scenario significantly reduces the tumor cells and CAF. The application of anti-PD1 reduces the resident CAF population and drastically reduces the tumor cell population. The population refer to the median population in the immune-dominated group (S6 Fig). Furthe the line bars indicate the 25% and 75% quartiles of the population within the immune-dominated scenario. (e) The post-ICI tumor cell population is proportional to the tumor-promoting role (via paracrine interaction) of the remaining CAF population.

doi: https://doi.org/10.1371/journal.pcbi.1013127.g005