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Sex differences in the association between tumor growth and T cell response in a melanoma mouse model

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Abstract

Epidemiological evidence suggests that females have an advantage over males in cases of melanoma incidence, progression, and survival. However, the biological mechanisms underlying these sex differences remain unclear. With the knowledge that females generally have a more robust immune system than males, we investigated sex differences in melanoma progression in a B16-F10/BL6 syngeneic mouse model. We observed significantly less tumor volume and growth rate over 14 days in female mice compared to male mice. Furthermore, higher populations of CD4+ and CD8+ T cells, which indicate adaptive immune responses, were found in the circulating blood and tumors of females and corresponded with less tumor growth, and vice versa in males. Our results highlight a mouse model that represents melanoma progression in the human population and displays a higher immune response to melanoma in females compared to males. These findings suggest that the immune system may be one of the mechanisms responsible for sex differences in melanoma.

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Acknowledgements

This work was supported by grants from the Congressionally Directed Medical Research Program Award CA171123 (S.G.), in part by the National Institutes of Health R01ES030113, R21CA227381 (S.G.) and Melanoma Research Alliance Team Science Award (S.G.).

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Authors and Affiliations

  1. Department of Pharmaceutical Sciences, College of Pharmacy and Pharmaceutical Sciences, Washington State University, PO Box 1495, Spokane, WA, 99210-1495, USA

    Panshak P. Dakup, Kenneth I. Porter, Alexander A. Little, Hui Zhang & Shobhan Gaddameedhi

  2. Sleep and Performance Research Center, Washington State University, Spokane, WA, USA

    Shobhan Gaddameedhi

Authors
  1. Panshak P. Dakup
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  2. Kenneth I. Porter
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  3. Alexander A. Little
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  4. Hui Zhang
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  5. Shobhan Gaddameedhi
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Contributions

Concept and supervision by SG. Animal studies, assays, and analysis performed by PD, KP, AL, and SG. Immunology expertise, training, and antibodies from AL and HZ. Writing of the original draft by PD. Reviewing and editing by all authors.

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Correspondence to Shobhan Gaddameedhi.

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262_2020_2643_MOESM1_ESM.jpg

Fig. S1—Determination of B16-F10 tumor growth rates. A linear regression model was fit to the tumor growth data for each sex from Fig. 1 and generated the equation y = mx + b, where m = slope. The difference in the slopes was calculated using one-way ANOVA to test the null hypothesis that the slopes are identical. Supplementary material 1 (JPEG 40 kb)

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Dakup, P.P., Porter, K.I., Little, A.A. et al. Sex differences in the association between tumor growth and T cell response in a melanoma mouse model. Cancer Immunol Immunother 69, 2157–2162 (2020). https://doi.org/10.1007/s00262-020-02643-3

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