Everolimus is an inhibitor of mammalian target of rapamycin, approved in patients with metastatic renal cell carcinoma. Besides, mammalian target of rapamycin inhibition has the ability to modulate T-lymphocyte homeostasis. Here, we report the case of a metastatic renal cell carcinoma patient treated with everolimus who presented unexpected prolonged tumor response. The monitoring of immune responses showed strong antitumor T-cell activation at the time of disease control, whereas a profound immunosuppression occurred when tumor progressed. Thus, a change of immune functions is associated with everolimus treatment. Our observation suggests that everolimus could shape immune responses, which in turn could contribute to its efficacy.