Tumor reductive therapies and antitumor immunity

Abstract

Tumor reductive therapy is to reduce tumor burden through direct killing of tumor cells. So far, there is no report on the connection between antitumor immunity and tumor reductive therapies. In the last few years, a new category of cancer treatment, immunotherapy, emerged and they are categorized separately from classic cytotoxic treatments (chemo and radiation therapy). The most prominent examples include cellular therapies (LAK and CAR-T) and immune checkpoint inhibitors (anti-PD-1 and CTLA-4). Recent advances in clinical immunotherapy and our understanding of the mechanism behind them revealed that these therapies have a closer relationship with classic cancer treatments than we thought. In many cases, the effectiveness of classic therapies is heavily influenced by the status of the underlying antitumor-immunity. On the other hand, immunotherapies have shown better outcome when combined with tumor reductive therapies, not only due to the combined effects of tumor killing by each therapy but also because of a synergy between the two. Many clinical observations can be explained once we start to look at these classic therapies from an immunity standpoint. We have seen their direct effect on tumor antigen in vivo that they impact antitumor immunity more than we have realized. In turn, antitumor immunity contributes to tumor control and destruction as well. This review will take the immunological view of the classic therapies and summarize historical as well as recent findings in animal and clinical studies to make the argument that most of the cancer treatments exert their ultimate efficacy through antitumor immunity.

Keywords: cancer immunotherapy; cancer reductive therapy; immune checkpoint therapy; targeted therapy; tumor antigen.

Figure 1. The initiation, establishment and function of a concomitant antitumor immunity in cancer patients

Tumor growth releases antigen and induces innate inflammation, stimulates concomitant antitumor immunity, which contributes to control the primary tumor and eliminates metastasis.

Figure 2. The immunological views of cancer surgery

Surgery may cause antigen clearance and antitumor immunity. It could also be tumor stimulatory. Surgery may have different outcomes because of the interaction of various effects.

Figure 3. The immunological view of chemotherapy

Classic cytotoxic drugs and modern targeted therapy contributes to antitumor immunity. Chemotherapy is, in essence, immunotherapy.