Immunogenic chemotherapy: great potential for improving response rates

Abstract

The activation of anti-tumor immunity is critical in treating cancers. Recent studies indicate that several chemotherapy agents can stimulate anti-tumor immunity by inducing immunogenic cell death and durably eradicate tumors. This suggests that immunogenic chemotherapy holds great potential for improving response rates. However, chemotherapy in practice has only had limited success in inducing long-term survival or cure of cancers when used either alone or in combination with immunotherapy. We think that this is because the importance of dose, schedule, and tumor model dependence of chemotherapy-activated anti-tumor immunity is under-appreciated. Here, we review immune modulation function of representative chemotherapy agents and propose a model of immunogenic chemotherapy-induced long-lasting responses that rely on synergetic interaction between killing tumor cells and inducing anti-tumor immunity. We comb through several chemotherapy treatment schedules, and identify the needs for chemotherapy dose and schedule optimization and combination therapy with immunotherapy when chemotherapy dosage or immune responsiveness is too low. We further review tumor cell intrinsic factors that affect the optimal chemotherapy dose and schedule. Lastly, we review the biomarkers indicating responsiveness to chemotherapy and/or immunotherapy treatments. A deep understanding of how chemotherapy activates anti-tumor immunity and how to monitor its responsiveness can lead to the development of more effective chemotherapy or chemo-immunotherapy, thereby improving the efficacy of cancer treatment.

Ultrasound -Induced Thermal Effect Enhances the Efficacy of Chemotherapy and Immunotherapy in Tumor Treatment

“… 54–56 Chemotherapy can induce immunogenic cell death (ICD) and elicit the immune response, rendering it a common adjunct to PD-L1/PD-1 checkpoint blockade immunotherapy in clinical settings. 57 , 58 The infiltration of CD8 + T cells following the combination of US irradiation, chemotherapy, and immunotherapy was investigated by collecting tumor tissues for FCM analysis 7 days after treatment. The results demonstrated a significantly higher proportion of CD8 + T cell infiltration in the groups E, F and H compared to groups C, D, and G ( Figure 5A and B ).…”

Potential of Natural Phenolic Compounds against Doxorubicin-Induced Chemobrain: Biological and Molecular Mechanisms Involved

“…As a matter of fact, these drugs are still among the most frequently administered ones when we consider therapy for hematologic tumors, as well as for a large number of solid tumors including lung, breast, ovarian, bladder, thyroid, gastric cancer and neuroblastoma [31]. Moreover, recent observations have shown that chemotherapeutics act not only by exerting direct cytotoxic activity on highly proliferating cancer cells but also by inducing immunogenic cell death [32,33]. This means that these drugs have the capacity to strengthen the immune response that is naturally, but ineffectively, carried out against tumors.…”