You are all used to me breaking in with other topics I want to update or discuss. So, here’s a break in immunotherapy (though I know we JUST got started with that), to update you on my experiments with weight training after FOUR months of a new regimen.

If you recall, around mid-June, my current body pump instructor took me aside and told me I was lifting too much weight. She gave me a different regimen that included minor reductions in the weight loads for several of the tracks. Because I trusted her instruction (she was the type of instructor to go around the class and actually correct students’ forms), I decided to try it for at least 3 months. My biggest worry, as any person serious about their exercise would be, was that the reduction in exertion would result in not getting the maximum out of my workout. In fact, it’s the same worry I had when I began to reduce my maximum heart rate in spin class; I was afraid that the fewer calories burned per class would result in weight gain or reduced muscle tone. FYI, that has NOT been the case at all.

So with that, I have completed now four months of this new training regimen. And here are my conclusions, which of course, are highly personalized to me and in no way mean this is what will work for everyone across the board.

It’s pretty straightforward: my brain felt it had permission to use reduced weights because of the credible source (e.g., body pump instructor), which then lead to me perceiving that my pump workouts, which I always dreaded and were always always (ALWAYS) so tough to get through, would now be easier. From this starting point, my mind put me at a more positive framework.

With this mental shift, I found that focus was taken away from the FODW (Fear Of Dropping the Weights) and the FONFR (Fear Of Not Finishing Reps). More brain power could now be devoted to actually focusing on and improving the form, as well as implementing other good habits learned from other classes like finally learning to engage my core (I never knew what that meant until my core got strong enough from pilates class). It was crazy, but I could squat lower without bowing and watch where my knees were and keep my back straight AND breathe...all at once.

Another thing, my body weight has stayed constant, just as before when I was lifting heavier weights.

Finally, I perceive no major difference in my strength.

What I really want to encourage is to listen to what some instructors are actually saying. Be receptive to what the instructors are suggesting, be open to experimentation, and be more mindful of form than amount of weight or keeping up with the reps. At least, do this until your form is as close to perfection as you can get it, or find the compromises that allow you to achieve perfect form, like reducing weights. The payoff is much healthier and equally as challenging.

Let’s get to the heart of the checkpoint blockade immunotherapy story and try to clarify some points that I left ambiguous in the previous post.

For review, we had depicted what happens when Antigen Presenting Cells that have encountered foreign bodies in its surveillance, “present” foreign material to the T cell (see top row image). The T cell can tell that what it is being presented is NOT “self;” this step was called “priming.” At the same time the T cell is recognizing what the APC is presenting it, it DOESN’T know that the APC itself is one of the good guys. In theory then, the T cell would turn around and attack the APC.

But it doesn’t attack, because the APC also binds another receptor on the T cell called the CTLA-4 (Cytotoxic T Lymphocyte Associated Protein–4). This binding event serves to turn on the T cell’s internal brakes, thereby stopping it from attacking the APC.

Now, let’s turn to the second row images. If the T cell encounters a tumor cell, it binds as it did to the APC through the MHC–TCR, because the tumor cells possess the MHC like the APC has. The tumor cell also possesses a receptor, called PD-L1 in the illustration, that applies the braking system of the T cell like the CTLA-4 did for the APC. Thus, in a normal setting, the tumor escapes from being destroyed by the T cell because it too can signal the T cell to “HEAL!”

So once again, the T cell recognizes the tumor as foreign, but is shut down by the binding of its PD-1.

In checkpoint blockade therapy, an antibody (red Y-shaped object in illustration) is created to specifically bind with PD-1–PD-L1. Therefore, when the T cell encounters the tumor cell and recognizes it as foreign or non-self through the binding of its TCR, the antibody blocks the interaction between PD-1 and PD-L1. When this happens, the tumor can’t shut down the T cell’s attack mode.

So guess what it does? IT ATTACKS, and destroys the tumor!

This is the very very basic mechanism behind checkpoint blockade. There are so many more complexities that frankly are above my pay grade to explain, so, anyone who has knowledge to correct and add to this, please let me know!