The physics of it is that yes, it does change the way the speaker sounds. Now, if it is for the better, or if it is worse is 100% subjective.
Combo amps with open backs have a more di-pole acoustic output. I.E. it sends energy nearly equally forward and backward. The amp inside the combo does reflect and garble up some of that rearward energy, and the rearward energy also is impacted by the size of the enclosure and how the cabinet is built around the speaker. The energy is reflected off the walls of the inside of the cabinet, which does have an impact.
Some people really love combos because the open-back design lends to exciting more of the space they are playing in. That added interaction is what makes combos seem bigger than they really are, and is probably why they are the most popularly recorded style of amp ever. They do a thing, that closed-back designs do not.
Closed-back cabinets are more hit and miss. The cabinet should be designed within the Thiele-small parameters of the speaker/s to really perform their best, but many are simply made to a convenient size. If you change the speaker, again you change the performance characteristics. I have a love-hate with closed-back cabinets. In the single speaker variety, they are very narrow dispersion, the sound is very direct and in the room, they sound like a very small point source. This is good and bad. Great for micing and keeping stage levels down, bad if you are a guitarist that relies on stage volume and moves around a lot. Larger 4x12" cabinets are very beamy ( a nature of the way the speakers are arranged ), but sound HUGE, and you generally get better coverage ( as opposed to a single speaker cabinet ). The phase interaction between the speakers is a large part of what makes a 4 x 12" cabinet have its thing. Where you are off-axis it will have an effect on the sound you hear, but it is not necessarily bad, just different, which makes it a good tool for room micing them, there are an infinite number of places to put a mic that you can get a different sound.
This leads me to what I feel is the ultimate compromise. 2 x 12" closed-back cabinets have a thing they do. They have just enough oomph and power to move air and get the sound out, don't have a crazy amount of phase issues, and sort of hit in between a combo and a 4 x 12" monster. I am not a fan of open-back designs, mainly because I play in smaller spaces these days, so I don't want the room all excited with my guitar, I tend to go with 2 single 12" ported cabinets, or a 2 X 12" cabinet. I have laid my 4 x 12" cabinet to rest in the garage for practicing. The other nice thing about 2 x 12" is that you can orient the cab vertically or horizontally, which gives a different sound and yet another option with a single cabinet.