Some older reports are addressing this question (e.g. J Natl Cancer Inst. 1985 May;74(5):1085-8. Hormonal influences on growth of B16 murine melanoma.

Simon SR, Ershler WB). Despite differences in the male and female innate and adaptive immune responses tumor growth is comparable. However, in my own experience female mice are more suitable, particular if you are using a s.c. model, since males are more aggressive and thus prone to infractions of the tumor.

Most important is to choose the best B16 subline as these show major differences both in their growth, metastatic potential, induction of immune responses etc.. However, not all the 'labels' of the B16 lines 'on the market' are correct! Thus, always ask for a detailed description of the in vivo behavior of the respective cell line - which may include differences in growth in males or females ;-)

Dear Pedro, happy to see you again! Obviously, it doesn't matter. You can successfully transplant melanoma B16 cells (as well as another in vivo propagated transformed cell lines) into male and female B6 or F1(DBA/2 x C57BL/6) mice . Differences on H-Y are too weak and have no significant influence.

Thank you Dmitry! That makes my life much easier.

Sorry that I have not yet uploaded the pdf from our latest review as you requested but I don't yet have the final version of the paper. Will put it up as soon as possible!

Thanks, Pedro! Hope to see your review, when it will be available to you! Good luck!

You can use males or females, does not matter.

We have been working with this mouse model and, although their basic immune profile is different in males versus females, the clinical evolution of melanoma is statistically the same.

We are working a subcutaeous mice model of melanoma using B16/F0 or F10 tumor cell sublines and we note a higher and aggresive melanoma development in female. At the present web are analizing several parameters and result to publish a paper

My rationale for asking was that if the cell line is male then it can potentially present Y-chromosome antigens in a female, making it slightly more immunogenic (once the barriers of immunosuppresion are broken). Yet, there should be plenty of neo-antigens in melanoma like B16 so maybe having a few more will not make a difference.

I agree with Pedro

A very good question, as once Tamoxifen was included in the therapies for Advanced Melanoma, because of the presence of hormone receptors in Melanoma cells, however, male and female mice do have an hormonal environment, even when it's different, and things such as metabolization of Steroid Hormone precursors, or hormones of low activity, into very active ones, such as E2, in normal fat tissues is to be taken into account, as it has an importance, for example, in Breast cancer and Endometrial cancer patients, to cite the two more evident.

If I had the resources, I'd transplant the Melanoma line both in male and female mice, the putative differences in outcome may have a later translation to bedside, but I'm a clinician, not a lab person.

I'll follow closely this very interesting issue, thanks

Some older reports are addressing this question (e.g. J Natl Cancer Inst. 1985 May;74(5):1085-8. Hormonal influences on growth of B16 murine melanoma.

Simon SR, Ershler WB). Despite differences in the male and female innate and adaptive immune responses tumor growth is comparable. However, in my own experience female mice are more suitable, particular if you are using a s.c. model, since males are more aggressive and thus prone to infractions of the tumor.

Most important is to choose the best B16 subline as these show major differences both in their growth, metastatic potential, induction of immune responses etc.. However, not all the 'labels' of the B16 lines 'on the market' are correct! Thus, always ask for a detailed description of the in vivo behavior of the respective cell line - which may include differences in growth in males or females ;-)

The question of Y-chromosome neo-antigen presentation is a sound one. We have transplanted B16 into both male and female mice, and at least in our hands, the results are equivalent. We test a dendritic cell vaccine targeting specific oncodrives (such as mutated BRAF), so it is a potent immune stimulus that may stifle subtle differences in immunogenicity between male and female species. I guess it depends on what you're trying to do exactly. 

B16 is derived from a male mouse (https://web.expasy.org/cellosaurus/CVCL_F936) so in theory it should be more immunogenic in female mice. It is interesting that in real experiments there is no difference.

You know Human Melanoma cell lines express or have influence from, Sex Steroid Hormone Receptors, Tamoxifen, a Selective Estrogen Receptor Modulator, was used sometimes to treat advanced Melanoma cases, so gender matters, in humans, but as tumor biology is not always same or similar between humans and rodents, data can't be carried over interspecies.

A recent article in 'Science' points why antidepresant drugs do not work same in mice and in human beings.

In the same line, 5-FU is absorbed and has an action in rodents' malignancies when given po, while not in humans

I'm not a lab man, never conducted animal lab research, so I ignore if there are enough and detailed enough data available on differences in tumor biology inside animal labs, and betwen animals and humans.

Thanks. Regards. Salut +

We have done B16 experiments in both male and female and in terms of serum biomarkers during melanoma development there are huge differences between sexes. If you are interested you can read our paper regarding "Sex differences....."

Dear Tanya, In the most strong model of sensitisation, H-Y incompatible skin grafts in C57BL/6 mice are rejected in 15-18 days. About the same time is necessary for transplanted melanoma B16 cells to kill mice of the same strain. The immune response doesn't start working immediately. Even in response to strong tumor transplant antigens, such as H-2 antigens, you will not be able to see an immune response until day 10. Thus, the growth of melanoma in vivo most of the time occurs without the pressure of the immune system.

Thank you Dmitry. This makes perfect sense for the models that follow B16 growth for up to 2 weeks, which indeed may be the majority of studies. But perhaps in tumor rechallenge setting, in mouse models of therapy where tumor growth may be delayed beyond the 2 weeks, and in studies of T cell specific responses to B16 antigens H-Y response in female hosts might be relevant.

Yes, if melanoma expresses H-Y antigens. There was interesting story of identification of H-Y antigens by serological methods and big discussion about results, because many findings could not be reproduced in other hands. This identification was difficult task.

Re: Tanya Bondar - H-Y story, as it has appeared in "Natural History of the Major Histocompatibility Complex" by Jan Klein, 1986.

Dear Dmitry, many thanks for this text. It was a joy to read, especially the presentation of different opinions and the term "paraserology".

Coming back to the original question, there is a report that growth of a cell line expressing H-Y antigen is better controlled in female mice and is T-cell-dependent: J Immunother. 2004 Sep-Oct;27(5):329-38.