Ho-ho-ho! Gather ’round, my curious elves, for a tale of the microscopic battleground within the wintry realm of metastatic renal cell carcinoma (RCC), where immune checkpoint inhibitors (ICI) are the magical sleighs delivering hope to those in need. Our scientific sleuths embarked on a quest to explore the expression of the ICI PD-L1, BTLA, and TIM-3, akin to checking who’s naughty or nice, but at the different cozy nooks of the tumor’s invasion front and its bustling center.

In a workshop of 44 stage pT1-4 clear cell RCCs, our researchers, with their trusty immunohistochemical tools, painted a picture of these molecules, much like I paint toys for all the good children. TIM-3, the most mischievous of the bunch, was found frolicking strongest at the invasion front, while BTLA preferred the normal tissue, showing only a faint presence in the tumor’s heart and edges. PD-L1, the shy one, was weakly expressed, peeking out only occasionally at both the center and the invasion front.

But wait, there’s more! When correlating with the list of clinicopathologic data, it was found that BTLA was bolder in ≥T3 tumors, and its presence at the tumor center was like receiving a lump of coal, correlating with a grimmer cancer-specific survival (CSS). PD-L1, while not as clear-cut, was also a bit of a Grinch, associated with worse CSS. TIM-3, however, seemed to have no significant effect on the survival story.

So, what does this festive fable tell us? The expression of these checkpoint receptors is as varied as the snowflakes in a blizzard, both within and between tumors. For the clinicians in their workshops, it’s a reminder to sample different tumor locations, like placing presents under every part of the tree, and to consider multiple inhibitions of different checkpoint receptors, like mixing hot cocoa with marshmallows, to potentially increase the therapeutic success.

And with that, my dear elves, let’s continue our work, for there are many more mysteries to unravel in the quest to bring joy and health to all! 🎅🔬