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TheReigningSupreme t1_ivwrj0s wrote

(If someone can tell me how to host or post the article, I'll try!)

Taken from article:

Highlights

• Tumor-specific T cells are necessary but not sufficient for therapeutic efficacy

• IV vaccination promotes tumor regression by remodeling the TME

• Systemic IFN-I following IV vaccination alters intratumoral Chil3+ monocytes

• Enrichment of human homologs of Chil3+ monocytes is associated with worse outcomes

Limitations

There are several limitations to this study. First, the key observations were performed in murine tumor models that may not accurately reflect the tumor immune microenvironment in humans. Key features including tumor architecture, vascularization, growth rate, and immune infiltrate may differ in patients when compared to a transplanted tumor in mice. Second, we have used two murine tumor models (MC38 and TC-1) that are both immune-inflamed tumors. As such, the findings of this study may not model immune-excluded or immune-desert tumors. Third, although we have performed experiments using IFNAR1 blocking antibodies to show that vaccine-induced IFN-I can modulate the Chil3+ monocytes in the tumor, we did not provide direct evidence that Chil3+ monocytes are responsible for suppressing the antigen-specific CD8+ T cells. Finally, the human TCGA data included in this study highlight LGG and ccRCC, two cancer indications where the enrichment of HuChil3 monocyte genes is associated with worse survival compared to pan monocyte genes; this observation may not be generalizable to all tumors. Nevertheless, despite these limitations we believe these data provide a translatable approach for using innate stimulation by intravenous vaccination to potentially improve T cell function in tumors that express such inhibitory profiles.

Declaration of interests

A.S.I., G.M.L., and R.A.S. are listed as inventors on patents describing polymer-based vaccines. A.S.I. and G.M.L. are employees of Vaccitech North America, which is commercializing polymer-based drug delivery technologies for immunotherapeutic applications. F.B. and S.M. are employees of Genentech, a member of the Roche group, which develops and markets drugs for profit

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personAAA t1_ivx3dun wrote

To explain some of this to lay readers. Cancers are weird. Everything from the shape and structure of them to how they get and structure the blood supply system. This paper and its subfield focus on the local immune environment of cancers.

Cancers somehow avoid being killed off by the immune system. Why the immune is not working on the cancer is a big question.

One thing being tried with this vaccine approach is teaching the immune system hey this actually is cancer.

This paper has for IV given vaccines, the immune system is working two ways to fight cancer. The innate immune system is working in the local tumor environment. T cells are boosted and fight the cancer better.

This study was done in mice, so don't get hopes up too much. How much different between lab mice tumors and a particular human cancer is a big question.

Cancer is better understood as a collection of diseases. The genotype of the cancer, the location, and tissue of origin all matter. Not all cancers are as scary as others. Don't panic if you here the c word. Find out what it is more in depth before worrying too much. Stressing yourself out wouldn't help.

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zv88909 t1_iw0432l wrote

Mouse models are actually pretty good, and the transplantable tumor models like mc38 are more aggressive than essentially any human cancer. The huge issue with mouse models is people starting the study very early after establishing the tumor in mice, when the tumor is quite weak really.

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