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16 The Dynamics of Tumor Microenvironment and Therapeutic Targets
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25
2
Shaping Cancer
Influence of Immune Cell
Dynamics in the Tumor
Microenvironment
Ananya Jana, Cameliya Singha Roy,
and Sanjima Pal
2.1 INTRODUCTION
Cancer is the most prominent global healthcare challenge with high incidence and
poor prognosis. Cancer cells create complex networks of interactions with immune
cells directly (cell-to-cell) and via humoral mediators (i.e., antibodies, chemokines,
cytokines). This dynamic microenvironment undergoes constant modication, which
can lead to changes in the immunophenotype that might explain cancer progression,
dedifferentiation, and resistance to treatment. The tumor immune microenvironment
(TIME) is an integral part of the tumor development and progression and comprises
a complex network of tumor cells, various immune cells, and stromal cells. Over the
past few decades, strategies aimed at modulating the TIME have made signicant
strides in cancer treatment. The host immune response to cancer is widely under-
stood through the “three Es” model: elimination, equilibrium, and escape (Mittal
et al. 2014). In the equilibrium phase, immune cells initially suppress tumor growth
by eliminating or rendering tumor cells dormant. There is substantial evidence of
immune-mediated antitumor effects through cytotoxic activity, antibody production,
immunological memory, and antigen cross-presentation. However, the host immune
system eliminates most malignant cell precursors and contains microscopic neo-
plasms in a dynamic equilibrium, thereby preventing cancer outgrowth. Eventually,
aggressive tumor cells outperform immune cells by employing sophisticated strate-
gies, encapsulated in the “three Cs” model—camouage, coercion, and cytoprotec-
tion. Cancer cells utilize immune editing to “camouage” themselves from immune
system detection, rendering them less immunogenic. Additionally, malignant cells
“coerce” immune effector cells, either directly or indirectly, impairing their func-
tion. Simultaneously, prolonged interactions between neoplastic cells and immune
cells lead to hyperactivation and exhaustion of immune cells, enabling tumor cells
to escape immune surveillance. Furthermore, cancer cells establish additional “cyto-
protection” mechanisms to shield themselves from the cytotoxic effects of immune
responses. This collective phenomenon, where cancer cells evade and counteract the
DOI: 10.1201/9781003405023-2