Chemotherapy and Immune Response, Complex Therapeutic Terrain

Chemotherapy-Stimulated Immune Response: An Open Debate

Jonathan Goodman, Cancer Therapy Advisor

Chemotherapy and Immune Response, Complex Therapeutic Terrain

“A recent review suggested that chemotherapy may prime cancer to respond to checkpoint inhibition.1 According to the review, which was published in the Annals of Oncology earlier this year, this may occur for a variety of reasons, depending primarily on the mechanism of action of the chemotherapy in question. 

In the past, these predictions may have been surprising to researchers in oncology, as chemotherapy was previously thought to be immunosuppressive. Yet, the authors argue, the effects of chemotherapy can “induce favorable immunogenic conditions within the tumor microenvironment, which may be difficult to achieve by just targeting immune cells.” 

In this setting, chemotherapy functions as the first part of a 2-stage evolutionary trap, where in the first stage clinicians actively select for a tumor microenvironment in which checkpoint blockade is most likely to be effective. With cyclophosphamide, for example, immunogenic cell death may be induced, and the drug may lead to dendritic cell homeostasis.2,3 Both are favorable immunomodulatory effects that may lead to an improved immune response —especially, it appears, when checkpoint blockade is used. 

A recent editorial published in the Annals of Oncology, however, suggests that the notion of turning “cold” tumors “hot” may be a misconception.4 This, according to a study author, Thomas Helleday, PhD, professor of translational oncology and director of the Sheffield Cancer Centre at the University of Sheffield, England, is for several key reasons, each of which has to do with the selective processes caused by chemotherapeutics.“


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Goals for improving cancer treatment in children

Ushering in the next generation of precision trials for pediatric cancer

Steven G. DuBois, Laura B. Corson, Kimberly Stegmaier, and Katherine A. Janeway

Science (Review article)

Goals for improving cancer treatment in children

Abstract—Cancer treatment decisions are increasingly based on the genomic profile of the patient’s tumor, a strategy called “precision oncology.” Over the past few years, a growing number of clinical trials and case reports have provided evidence that precision oncology is an effective approach for at least some children with cancer. Here, we review key factors influencing pediatric drug development in the era of precision oncology. We describe an emerging regulatory framework that is accelerating the pace of clinical trials in children as well as design challenges that are specific to trials that involve young cancer patients. Last, we discuss new drug development approaches for pediatric cancers whose growth relies on proteins that are difficult to target therapeutically, such as transcription factors.


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Non-small cell lung cancer prognosis from blood samples

Tumor DNA in blood may predict response to lung-cancer immunotherapy

Non-small cell lung cancer prognosis from blood samples. Genome Media.

Blood tumor mutational burden may give insight into which patients with non-small cell lung cancer (NSCLC) may benefit from therapy with anti-programmed cell death 1 (anti-PD-1) and anti-programmed cell death ligand 1 (anti-PD-L1) monoclonal antibodies, according to Chinese researchers.

A considerable number of patients with advanced cancer may not be able to provide sufficient tissue for molecular testing to guide treatment decisions, Dr. Jie Wang of Peking Union Medical College and colleagues note in JAMA Oncology, online February 28. However, rather than use tumor mutational burden measured by whole-exome sequencing or cancer gene panel, the researchers sought to determine the utility of using circulating tumor DNA in blood.


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