To address this need we developed a computational model capturing the current understanding of how individual metastatic tumor cells and immune cells sense and contribute to the tumor environment, which in turn enabled us to investigate the complex, collective behavior of these systems.

Surprisingly, we discovered that tumor escape from immune control was enhanced by the existence of small differences (or heterogeneities) in the responses of individual immune cells to their environment, as well as by heterogeneities in the way that cells and the molecules they secrete are arranged in space.

This prediction also dovetails with observations that variability in the location, density and type of tumor-infiltrating immune cells has prognostic value [28].

Based on our investigations, we would hypothesize that elevated spatial heterogeneity in the TME might correlate with severity of tumor-associated immune dysfunction or intransigence to therapeutic intervention, and it could be informative to investigate whether metrics defined on such a basis (e.g., degree of spatial clustering in tumor-infil-trating immune cells , which may be quantified histologically in tumor biopsy samples) might have prognostic value.

Growth and persistence of a tumor is influenced not only by the intrinsic proliferative capacity of the cancer cells, but also by the complex ecosystem of cells, signaling molecules and vascula-ture surrounding the tumor, which collectively comprise the tumor microenvironment (TME) [1,2] An important feature of the TME is the important role played by non-tumor cells, including both immune cells and stromal cells, in promoting tumor proliferation by contributing to immune evasion, induction of angiogenesis, and other hallmarks of cancer [3,4].

One physiological trait that may play a key role in such a shift is the capacity of immune cells to adopt different functional states in different environments, which is perhaps best illustrated by a cell type that strongly affects the early TME—the macrophage.

Thus, interactions between functionally heterogeneous immune cells , the tumor, and the TME may collectively drive dynamics of the early TME immune network.

Both containment of cytokine action in narrow junctions between immune cells (immunological synapses) and global signaling throughout entire lymph nodes have been proposed, but the conditions under which they might occur are not clear.

The adaptive immune system fights pathogens through the activation of immune cell clones that specifically recognize a particular pathogen.

Tight contacts, so-called immunological synapses, of immune cells With cells that present ‘digested’ pathogen molecules are pivotal for ensuring specificity.

First, we analyzed polarized signaling across narrow junctions — immunological synapses — between immune cells (nm scale).

In contrast to immune cell signaling with a typical time scale of many hours during which diffusive gradients reach steady state, the transient behavior on shorter time scales is of particular interest for morphogen gradients [51,54].

In our simulations, the spatial distribution of cytokine secretion and uptake within a population of immune cells had a huge impact on the cellular response, generating multiple layers of plasticity that can be exploited for appropriate regulation of immune responses.

Immunological synapses are formed between immune cells by surface proteins after antigen recognition [15,16,19].

CD25 is often used as an activation marker of T cells, because it precedes proliferation of Th cells and subsequent recruitment of effector immune cells [30,38].

Antibodies are one of the central mechanisms that the human immune system uses to eliminate infection: an antibody can recognize a pathogen or infected cell using its Fab region While recruiting additional immune cells through its PC that help destroy the offender.

These effector functions are mediated by the combined ability of an antibody’s Fab to interact with the antigen and its PC to interact with a set of FcR eXpressed on innate immune cells .

Furthermore, the logistic regression model enables straightforward identification of the key contributors, and points toward feature roles consistent with known IgG and innate immune cell biology.