Two decades ago, when I started my postdoc research in genetically engineered mouse (GEM) model of melanoma, I did not understand that the field did not sound promising at that time. First of all, we have very little knowledge in melanoma genetics. People complained that the melanoma we created in mice did not look like human melanoma, or we did not know what that thing was.

Second, the rise of targeted drugs, like BRAF inhibitor, brought a new hope. An idea became very popular: we can take a melanoma tissue from a patient, implant it in mice, and test their response to multiple targeted drugs, so as to find the best combination, and use it in the particular patient to cure her/his melanoma. This concept, "co-clinical trial on patient-derived xenograt (PDX) in mice", promoted the founding of quite a few companies ready to run such service for cancer patients and oncologists. There is no place for mouse melanoma models in such idea.

For a few years, things did not change too much. We made GEM models of melanoma but found difficulties to publish them. I remember that in a meeting held in Amsterdam, a young girl approached my poster as I took it down from the board. She said to me, "Sorry, I am the editor who rejected your manuscript", which was submitted to a high-profile journal. She promised to take a look again if I could add some clinical data to support the mouse results. I couldn't, and it continued that no one cared about our mice.

That was in the spring of 2010. In August, a real game changer in melanoma therapy emerged: Jim Allison and his team published the five-year clinical trial results of treating melanoma with Ipilimumab (immune checkpoint inhibitor, anti-CTLA4). Previously, the five-year survival rate of metastatic melanoma was close to zero. My jaw dropped when I looked at the survival curve: 20% after five years, and the outcome was stable after 2 years. From zero to 20%, this was a impossible jump made real!

Since the paper stunned the field of cancer research, My PI started to receive emails like this: Your mouse melanoma models have normal immunity, right? They sound a good model to test immunotherapy. May I get some breeding pairs? We started to send our mice to a lot places, and soon my mice traveled to much more countries than I have ever been. The mouse shipment job kept us very busy. One day, my PI decided it was enough. We should use our own mice to do research in melanoma immunotherapy. Before that, I had never spent one minute to study immunology, in school or in training.

In a few years, the cost of next generation sequencing dropped significantly, the omics data of both human and mouse melanoma accumulate in light speed. This makes the comparison between human and mouse melanoma possible. Meanwhile, melanoma as a relative rare cancer become the poster child of immunotherapy. Together, they greatly promote the generation and use of GEM melanoma models. In scientific research, you could not plan everything. I have to say, Jim Allison and our mice changed my career path forever.