Nature's "negative energy" of the tumor is much stronger than you think.

T-cells play a vital role in anti-tumor immunity, and many tumor immunotherapy techniques are currently focused on retrofitting T-cells, especially those with CD8 plus in tumors.
under normal circumstances, these cells are supposed to take on the responsibility of killing tumor cells, but recent studies have shown irreversible dysfunction of cytotoxic T cells in tumor micro-environments.
effects of anti-tumor immunity on the efficacy of tumor immunotherapy should not be ignored, unfortunately, there is still a lack of systematic research on how tumors affect systemic immunity.
most studies focus only on a single, specific point-in-time immune state, ignoring that tumor development is a dynamic process.
Even though many immunotherapy and vaccines are looking for ways to stimulate new immune responses in cancer patients, little is known about how the tumor itself affects the process, and it is not clear whether there is a persistent immune effect in the body when the primary tumor is successfully removed.
in addition to the tumor "microenvironment", the "macroenviroment" outside the tumor will inevitably have an impact on immunotherapy.
, Matthew H. of the University of California, San Francisco. Spitzer and his team, who published an article entitled "Systemicdysfunction and Plasticity of the immune macroenvironment in cancermodels" on NatureMdecine, found that the effects of tumors on the body's immune system are systemic, that the presence of tumors leads to a decrease in overall immunity and weakens the body's response to new immune stimuli, and that tumor removal can reverse this phenomenon.
Figure 1 Nature Medicine volume 26, pages1125-1134 (2020) Systemic immune tissue changes with tumor type First, the researchers used mass spectrometrative cytometology to analyze immune cell subtotypes in tumor models constructed by eight different tumor cell linees, and found that the tumor microenn environment The composition of the tumor was significantly different between different tumor models, in which tumor-related macrophages and other cd11bhigh myelin source cell subsystys occupied a clear dominant position, especially in the MC38 colorectal cancer model and SB28 glioma model, where there were relatively few adaptive immune cells.
and models of LMP pancreatic cancer tumors and Braf melanoma showed more acidic granulocytosis.
B16-F10 melanoma and three breast cancer models (4T1, AT3 and MMTV-PyMT) showed lower immune cell abundance, but were characterized by higher immune cell diversity.
, there are huge differences between different tumor immune micro-environments.
2 The immune micro-environment of different tumors varies greatly, will the immune status of the whole body change due to tumors? They analyzed the immune components of tumor drainage lymph nodes, bone marrow, blood and spleen and found that there were subtle differences between immune cell types between tumor models, but different tumor models of the same tumor type showed a surprising consistency.
is even more surprising that while SB28 gliomas are located in parts of the brain, they significantly affect the immune system throughout the body.
Figure 3 The difference in the state of immune cells in different tumor models with nonlinear changes in the proportion of immune cells with tumor growth Followed by researchers looking at the dynamic process of reshaping the system's immune system during the growth of breast cancer tumors, and they found that as the tumor progressed, the immune response was also in the process of constant change, and that the change was not strictly linear, not a uniform process of change.
Although changes in certain sub-groups are relatively continuous, such as an increase in neutral granulocytes or a decrease in CD4-T cells, it is more of a process of dynamic fluctuation, such as changes in CD8-T cells and changes in Treg.
4 The immune cells in the immune system change dynamically as the tumor progresses, does the tumor weaken the T-cell response Since tumor growth alters the tumor's immune environment, will this change affect the immune system's response to new stimuli? The type I immune response is closely related to the cytoimmune response and is thought to play an active role in the positive anti-tumor immune front, and to explore the effects of tumors on the type I immune response, the researchers gave healthy mice and AT3 lotus mice, respectively, to cause type I immunity. The antigen of the response, although the lotus mouse can also block the pathogen outside the spleen, but the cancer mouse CD8T cell differentiation, CD8-T cell proliferation and killing capacity are greatly reduced.
Figure 5 The response of T cells to pathogen infection decreased in mice with tumors because T cells in the outer blood did not completely lose power, but their ability to respond to the pathogen decreased, so the researchers speculated that this may be due to a decrease in the activity of the exosome antigen delivery cells (APC) affecting the activity of T cells in the outer blood, so they Two days after the pathogen infection, the expression of APC surface costulent molecules was analyzed, and it was found that APC surface expression was lower than that of APC surface expression in healthy mice, while the use of antibodies that stimulated APC active anti-CD40 did return the proliferation capacity of CD8T cells to the same level as in healthy mice.
Figure 6 APC activated drug can save T-cell functional removal tumor can save systemic immune changes Considering that T-cell activity can be removed from the tumor load environment after recovery, the researchers used surgery to remove the tumor, found that whether it is AT3, 4T1 or MC38 tumor model, removed tumor, spleen immune system ideographic and proliferation behavior is consistent with normal mice, indicating that the changes in systemic immunity was reversed! However, if there is a recurrence or metastasis of the tumor locally, the body's immune state will be in a transition state between normal mice and lotus mice.
The study further reveals the plasticity of the systemic immune system, as successful tumor removal can significantly reverse the collapse of the overall immune system, a finding that also provides guidance on the treatment of tumor immunotherapy, which may have a completely different outcome before or after surgery.
The small editor has said that we all know that the tumor is a bad guy, but did not expect it to be so means, affecting the local tumor micro-environment is not enough, but also try to destroy the whole body immunity, to the whole "big environment" are made earth-shaking, really sinister! It seems that there is still a long way to go in the fight between humans and tumors... References: Allen B M, Hiam K J, Burnett C E, et al. Systemic dysfunction and plasticity of the immune macroenvironment in cancer models. Nature Medicine, 2020: 1-10.QL. Yin Source: BioImmunology !-- end of content presentation -- !-- to determine if login is over.