Combining Immune Checkpoint Inhibitors With Conventional Cancer Therapy

Abstract

Immune checkpoint inhibitors (ICIs) have recently revolutionized cancer treatment, providing unprecedented clinical benefits. However, primary or acquired therapy resistance can affect up to two-thirds of patients receiving ICIs, underscoring the urgency to elucidate the mechanisms of treatment resistance and to design more effective therapeutic strategies. Conventional cancer treatments, including cytotoxic chemotherapy, radiation therapy, and targeted therapy, have immunomodulatory effects in addition to direct cancer cell-killing activities. Their clinical utilities in combination with ICIs have been explored, aiming to achieve synergetic effects with improved and durable clinical response. Here, we will review the immunomodulatory effects of chemotherapy, targeted therapy, and radiation therapy, in the setting of ICI, and their clinical implications in reshaping modern cancer immunotherapy.

Transcriptomic Profiling of Tumor-Infiltrating CD4+TIM-3+ T Cells Reveals Their Suppressive, Exhausted, and Metastatic Characteristics in Colorectal Cancer Patients

“…In conclusion, this study discloses some of the functional pathways of TIM-3 + TILs, which could improve their targeting in more specific therapeutic approaches in CRC patients.Vaccines 2020, 8, 71 2 of 17 checkpoints (IC) in suppression of anti-tumor immune responses to various malignancies provided new targets for immunotherapy. Despite the clinical efficacy of current available immunotherapies in cancer patients, a large proportion of CRC patients fail to respond mainly due to immune-cell mediated resistance [2].T-cell immunoglobulin and mucin domain containing 3 (TIM-3) is a member of mucin domain transmembrane protein family, which was initially recognized on CD4 + T helper 1 (Th1) and CD8 + T cytotoxic (Tc1) cells [3,4]. Later studies revealed that TIM-3 can also be expressed on other immune subsets, including T regulatory cells (Tregs) [5].…”

“…Vaccines 2020, 8, 71 2 of 17 checkpoints (IC) in suppression of anti-tumor immune responses to various malignancies provided new targets for immunotherapy. Despite the clinical efficacy of current available immunotherapies in cancer patients, a large proportion of CRC patients fail to respond mainly due to immune-cell mediated resistance [2].…”

Improving the efficacy of osteosarcoma therapy: combining drugs that turn cancer cell ‘don't eat me’ signals off and ‘eat me’ signals on

“…Previous investigators studied other combinations of conventional cytotoxic drugs and immunotherapies to achieve enhanced effects and overcome tumor resistance to classical chemotherapy (Yan et al, 2018). Since cytotoxic drugs may be either immunostimulatory or immunosuppressive (Nowak et al, 2006), it is important to find synergistic combinations and recognize antagonistic combinations.…”

Poly(cyclodextrin)‐Polydrug Nanocomplexes as Synthetic Oncolytic Virus for Locoregional Melanoma Chemoimmunotherapy

“…[ 7,9–11 ] As such, the potential for immunotherapy to synergize with traditional treatments has been proposed and clinically verified in multiple therapeutic settings. [ 12,13 ]…”