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 Tcells 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. ARTICLE HISTORY

Microparticle Depots for Controlled and Sustained Release of Endosomolytic Nanoparticles

“…Additionally, the timing, dose, and localization of immunomodulators plays a critical role in determining the magnitude and phenotype of the resultant immune response. 5,10,65,81,82 Yet, locally administered biomacromolecules, including nucleic acids, typically rapidly clear from the injection site, which not only limits local bioavailability but can also result in systemic distribution with an increased risk of toxicity. 37,39,80 These challenges have motivated the development of delivery technologies for controlled and sustained release of nucleic acid immunotherapeutics.…”

Experimental Combined Immunotherapy of Tumours with Major Histocompatibility Complex Class I Downregulation

“…With the advent of immunotherapy, new prospects have been opened up for successful cancer treatment. Increasing evidence shows that the efficacy of immunotherapeutic drugs can be enhanced by combined applications, which are believed to support the anti-tumor response at multiple sites [ 1 , 2 ]. Further advances include optimization of immunotherapy timing as well as deeper investigation and better understanding of tumor microenvironment biology [ 2 ].…”

Time-synchronized immune-guided SBRT partial bulky tumor irradiation targeting hypoxic segment while sparing the peritumoral immune microenvironment

“…The median follow-up was 11.8 months (range: [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22]. At the time of analysis, one patient (treated at "most favourable" time-position) had died 22 months after SBRT-PATHY because of causes other than cancer.…”

“…Currently, some studies have described an association between the radiation-induced lymphopenia with poor oncologic outcome, indicating that radiotherapy using large volumes and multiple daily fractions can lead to immunosuppression [8,9]. On the other side, some studies have shown potential therapeutic benefits by eventual ablation of regulatory ("suppressor") T cells with limited (single-dose) systemic therapies [10][11][12] given "at the right time" in order to selectively ablate those suppressor T cells while sparing the effector T cells. Thus, suggesting that the accurate timing of limited therapy may play a major role in treatment efficacy.…”