Rationale for Combining Immunotherapy with Chemotherapy

Abstract

Immunotherapy has usually been considered as an alternative to more traditional modalities. Moreover, it has previously been felt that chemotherapy is inherently immunosuppressive and not suitable for combining with immunotherapy. In this review, the concept of combining different modalities that result in cell death, such as radiotherapy and chemotherapy, with immunotherapy is explored. Tumors actively cause immune suppression which can be reversed by their removal but when this is not possible, enhancing the immune response with nonspecific immune stimulation can enhance the response to other modalities, such as radiotherapy and chemotherapy. Additionally, several chemotherapy agents at low doses selectively inhibit regulatory and suppressor cells.

Immune-modulating effects of bevacizumab in metastatic non-small-cell lung cancer patients

“…This observation has represented the bases for the combination of chemotherapy and/or radiotherapy with immune-adjuvant cytokines, active-specific immunotherapy and checkpoint inhibitors, in the treatment of human malignancies. 44–51 Previous results from us and others have already shown preclinical evidence that both chemotherapy and bevacizumab administration may affect MDICs and T reg s’ expansion, 50 , 51 whereas the present study demonstrate that it may also improve DC maturation and enhance CTL response, thus producing a more complex and efficacious antitumor effect. Moreover, the long-term effects of bevacizumab on the effector memory T cells and T h 1 lymphocyte subsets could have a positive impact on patients’ survival because the antitumor specific immune-response can be auto-sustained after the end of the treatment.…”

Acute skin reaction suggestive of pembrolizumab-induced radiosensitization

“…The time window for this combination therapy has not been clarified, although delivering immune checkpoint inhibitors shortly after radiation therapy may be the optimal therapeutic scheme [12]. In fact, radiotherapy should increase tumor-derived antigen presentation to effector T cells as well as inflammatory cytokine release, which may potentiate the antitumor immune response induced by these immunotherapeutic antibodies [7][8][9]. In addition, ionizing radiation may result in a specific loss of regulatory T cells [22].…”

“…It has been suggested recently that rational combination strategies with other anticancer agents, including radiotherapy, would enhance the immune response and extend the therapeutic effect of these immunotherapeutic antibodies [7][8][9]. As an example, radiation therapy may interact positively with immune checkpoint inhibitors in inducing a delayed proimmunogenic modulation with an enhancement in tumor antigen presentation or uptake by dendritic cells [8].…”

Trends in antiviral strategies

“…Related notions have been investigated with other viruses and different components of the immune response (Seiler et al, 2000;Li et al, 2005). However, additional model in vivo experiments with animals and clinical trials with patients are necessary to investigate the effectiveness of combined immunotherapeutic approaches, in line with related research in cancer therapy (Dalgleish, 2015).…”