The importance of correctly timing cancer immunotherapy

ABSTRACT

Introduction: The treatment options for cancer—surgery, radiotherapy and chemotherapy—are now supplemented with immunotherapy. Previously underappreciated but now gaining strong interest are the immune modulatory properties of the three conventional modalities. Moreover, there is a better understanding of the needs and potential of the different immune therapeutic platforms. Key to improved treatment will be the combinations of modalities that complete each other’s shortcomings.

Area covered: Tumor-specific T-cells are required for optimal immunotherapy. In this review, the authors focus on the correct timing of different types of chemotherapeutic agents or immune modulators and immunotherapeutic drugs, not only for the activation and expansion of tumor-specific T-cells but also to support and enhance their anti-tumor efficacy.

Expert opinion: At an early phase of disease, clinical success can be obtained using single treatment modalities but at later disease stages, combinations of several modalities are required. The gain in success is determined by a thorough understanding of the direct and indirect immune effects of the modalities used. Profound knowledge of these effects requires optimal tuning of immunomonitoring. This will guide the appropriate combination of treatments and allow for correct sequencing the order and interval of the different therapeutic modalities.

KEYWORDS:

• Cancer
• immunotherapy
• timing
• combination therapy
• immunomonitoring

Article highlights

• A profound understanding of the immune modulatory effects of current cancer therapies allows finding the optimal timing of multiple therapies with most clinical benefit for the cancer patient.

• Single treatment modalities can be successful at an early phase of disease while at later disease stages combinations of several modalities are required.

• Therapies applied before therapeutic vaccination are generally aimed at alleviation of immune suppression.

• Therapies provided concurrently or shortly after vaccination aim to potentiate the vaccine-induced immune response and to prevent normal immune regulation.

• Harmonization of immune monitoring helps paving the way for the rational design of immunotherapeutic combination strategies.

This box summarizes key points contained in the article.

Declaration of interest

EB Nejad is sponsored by a PhD grant from the Leiden University Medical Center.SH van der Burg is sponsored by a grant from the Dutch Cancer society. He also received support for his research on vaccines and as an advisor from ISA Pharmaceuticals. Furthermore, MJP Welters is supported by the Dutch Cancer Society while R Arens is sponsored by the Gisela Thier grant from Leiden University Medical Center. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

This manuscript is sponsored by the Dutch Cancer Society (2009-4400) and by the Leiden University Medical Center (LUMC).