Recognizing and managing on toxicities in cancer immunotherapy

Abstract

Over the past 4 years, cancer immunotherapy has significantly prolonged survival time of patients with prostate cancer, melanoma, lung cancer, and liver cancer, but its side effects are also impressive. Different types of the immune therapeutic agents have different on-target or off-target toxicity due to high affinity or weak specificity, respectively. Treatment toxicity spectrums vary greatly even in patients with the same type of cancer. Common toxicities are fevers, chills, diarrhea colitis, maculopapular rash, hepatitis, and hormone gland disorder; therefore, routine monitoring of thyroid function, liver function, renal function, and complete blood count are absolutely necessary once treatment begins. Some side effects are reversible, and can be processed through the standard medicines. However, serious toxicities are lethal, which should be frequently followed-up, identified at an early stage and immediately symptomatic treated by high-dose immunosuppressors. In this case, thereafter, the same agent should not be challenged again.

Myeloid-Derived Suppressor Cells as a Therapeutic Target for Cancer

“…As such, the success rates of immunotherapy are often unpredictable, having significantly variations with different cancer types and even within cohorts consisting of the same malignancy, for example in advanced ER+ breast cancer [39,40]. However since checkpoint inhibitors interfere with natural T-cell regulatory mechanisms, they can also lead to activation of autoreactive T-cells, resulting in autoimmune or autoinflammatory side-effects termed "immune-related adverse events" (irAEs) [41]. Despite the therapeutic success of checkpoint inhibitors for some cancer types, a primary challenge of this strategy for widespread anti-cancer application remains the low TILs presented by patients of many cancer types.…”

Comparing the effects of different cell death programs in tumor progression and immunotherapy

“…One can envision future combination therapies whereby induction of (a) maximally immunogenic tumor cell death is coupled with (b) modulation of tumor-associated antigen-presenting cells in conjunction with (c) immune checkpoint blockade to maximize CTL killing of any remaining tumor cells. Of course, coadministration of multiple antitumor drugs will need to be carefully balanced with the need to suppress systemic inflammation and off-target attacks, as highlighted by recent issues with neurotoxicity and cytokine release syndrome observed in some patients [158][159][160]. Nevertheless, the complex processes underlying tumor cell heterogeneity necessitate the expansion of treatments which can kill transformed cells that have escaped the selection pressures exerted by singular therapies to acquire immunotherapy resistance [161].…”

Thyroid dysfunctions secondary to cancer immunotherapy

“…Despite these few reports on thyroid dysfunctions following cancer vaccine treatment, phase III clinical trials have shown that the approved commercial cancer vaccines are overall safe, well tolerated, and associated with limited adverse events [96, 97]. Thyroid dysfunctions were reported only in 1 of 215 (0.46%) patients with stage IV melanoma [98], and in 1 of 48 (2.08%) patients with advanced renal cell carcinoma after treatment with Vitespen [99].…”