Pinning of Tumoral Growth by Enhancement of the Immune Response

Tumor growth is a surface phenomenon of the molecular beam epitaxy universality class in which diffusion at the surface is the determining factor. This Letter reports experiments performed in mice showing that these dynamics can, however, be changed. By stimulating the immune response, we induced strong neutrophilia around the tumor. The neutrophils hindered cell surface diffusion so much that they induced new dynamics compatible with the slower quenched-disorder Edwards-Wilkinson universality class. Important clinical effects were also seen, including remarkably high tumor necrosis (around $80\%–90\%$ of the tumor), a general increase in survival time [the death ratio in the control group is 15.76 times higher than in the treated group (equivalent to a Cox’s model hazard ratio of 0.85; $95\%$ confidence interval 0.76–0.95, $p=0.004$)], and even the total elimination of some tumors.

Figure 1

Power spectra of typical tumor contours: control group (above), treated group after 15 days of treatment (middle), and treated group after two months of treatment (bottom). The corresponding fits lead to ${\alpha }_{\mathrm{glob}}^{\mathrm{control}}=3.90\pm 0.15$, ${\alpha }_{\mathrm{glob}}^{15\mathrm{days}}=3.45\pm 0.10$, and ${\alpha }_{\mathrm{glob}}^{2\mathrm{months}}=3.19\pm 0.05$, respectively. The nontreated group has dynamics compatible with the MBE universality class (as in any type of tumor), while those of the group treated for 15 days are compatible with the QEW universality class corresponding to pinned elastic membranes moving in a disordered medium. Finally, if treatment continues, a decrease in the slope can be observed as an effect of the neutrophils.

Figure 2

Region $A$ is the host and region $B$ the tumor. In the bottom picture, the host-tumor interface is highlighted in red. Note how the neutrophils locate themselves to eliminate tumor cell surface diffusion.

Figure 3

(a) Hematoxylin-eosin composite of histological sections of a mouse tumor. The dark purple regions are proliferative regions of the tumor. (b) The necrotic regions appear darker in the NMR picture of tumor. The tumor is stained with gadolinium and appears in gray. White regions are fat. The necrotic core is black.