Comments on: Vertical transmission of tumors

By: Alejandro Montenegro-Montero

Alejandro Montenegro-Montero — Thu, 27 Aug 2009 14:42:38 +0000

Hi Ian,

Nice post.
I selected it as one of my “picks of the week” of posts aggregated at RB in molecular biology, over at my blog http://amontenegro.blogspot.com/2009/08/bacterial-freeloaders-early-metastasis.html
Cheers,
-A

By: iayork

iayork — Sun, 23 Aug 2009 20:09:08 +0000

One interesting element of vertical transmission of tumors is the lack of HLA expression on many tumors.

It’s variable depending on tumor type, but compelte loss of HLA on tumors is rather unusual — the most I’ve seen is about 35% for one tumor type (I can’t remember which one, though), with 5 – 20% being much more typical figures for complete loss. A partial loss, whether loss of heterozygosity or even isoform-specific mutations, is much more common, and that would leave much of the tissue-transplant-rejection aspect still functional. What’s more, those tumors that have completely deleted HLA, should be good targets for NK cells. I suspect this is telling us that a large component of tumor success is the specific immune suppression, in the form of TRegs and suppresssive antigen-presenting cells, associated with the tumor mass, and that this immune suppression does not cross the placenta.

Still, I agree that it’s a little surprising that vertical transmission isn’t more common, especially given the rate of maternal chimerism, as you and Song both point out.

By: David

David — Sun, 23 Aug 2009 03:36:02 +0000

One interesting element of vertical transmission of tumors is the lack of HLA expression on many tumors. In fact, I’m surprised we don’t see MORE vertical transmission of tumors because they are poor immunologic targets, the infant’s immune system is inherently deficient (most antibody is maternally derived for the first few months of life, and those antibodies should not mediate tumor rejection), and maternal cells readily cross the placenta and persist in the fetal/infant circulation for some time post-natally.

A related, also very interesting topic is twin/twin transmission of malignancy, predominantly leukemias. There is a big literature on this topic, especially as it relates to questions about the origins of childhood leukemia.

By: Song

Song — Fri, 21 Aug 2009 12:45:29 +0000

Thanks for the reference about the surgeon!

It’s very interesting that maternal-fetal transmission of tumors has been reported. I didn’t know that!

A colleague in my department has done some work on maternal-fetal microchimerism. It turns out that maternal cells migrate more or less routinely across the placenta and take part in the formation of many different tissues. I don’t know for how long the maternally derived cells persist, but it probably means that the fetus is in principle immunologically “able” to harbour maternal cancer cells as well.

For reviews on microchimerism, see e.g.
Bharath et al, Journal of Pediatrics. 142(1):31-35
Nelson, Trends in Molecular Medicine, Volume 8, Issue 3, 1 March 2002, Pages 109-113, doi:10.1016/S1471-4914(01)02269-9