Absolute Lymphocyte Count Predicts Abscopal Responses and Outcomes in Patients Receiving Combined Immunotherapy and Radiation Therapy: Analysis of 3 Phase 1/2 Trials

Chen, Fan; Verma, Vivek; Patel, Roshal R.; Barsoumian, Hampartsoum B.; Cortez, María Angélica; Welsh, James W.

doi:10.1016/j.ijrobp.2020.01.032

Cited by 78 publications

(53 citation statements)

References 18 publications

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“…A post hoc analysis of patients enrolled in several trials examining radiation therapy-immunotherapy regimens observed that the abscopal response rate was significantly higher among patients with higher ALC relative to more lymphopenic counterparts. 67 Additionally, a postradiation therapy ALC greater than the median correlated with superior progression-free survival and overall survival. As such, efforts to minimize radiation exposure to the circulating blood volume and to avoid lymphoid or myeloid-rich tissues (bone marrow, spleen, thymus, lymphatics) may help maintain a reserve of immune cells available to be recruited for antitumor immune responses.…”

Section: Tumor Burden As a Framework To Understand Radiation-induced mentioning

confidence: 96%

Radiation Therapy and the In Situ Vaccination Approach

Golden

Marciscano

Formenti

2020

International Journal of Radiation Oncology*Biology*Physics

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During the past century, from the advent of preclinical modeling to the establishment of clinical trials, the hypothesis that host defenses regulate tumor growth (posited and refined by leaders in the field of cancer immunity) has become accepted as a scientific pillar in oncology. Since the turn of the millennium, a search has been under way for the best therapeutic approach to reprogram the immune system to recognize tumor cells that have undergone "immune escape." This quest has led some to question conventional scientific views of tumor cell kill, including the role of host immunity in patients treated with radiation therapy. In the last two decades, evidence has accumulated that radiation therapy can effectively convert a potentially lethal cancer into an in situ personalized vaccine. Herein, we review the underlying mechanisms and maneuvers responsible for in situ vaccine production.

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Section: Tumor Burden As a Framework To Understand Radiation-induced mentioning

confidence: 96%

Radiation Therapy and the In Situ Vaccination Approach

Golden

Marciscano

Formenti

2020

International Journal of Radiation Oncology*Biology*Physics

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“…Similar results were reported for pre-RT ALC (30.3% vs. 7.8% respectively, p < 0.001). In Cox multivariate analysis, a lower post-RT ALC was associated with poorer PFS ( p = 0.009) and OS ( p = 0.026) [ 86 ]. Marciscano et al reported that irradiation of the draining lymph nodes impairs adaptive immune response mainly through chemokines expression and CD8 + T cell trafficking and thus may be deleterious when combined with immunotherapy [ 87 ].…”

Section: Increasing the Rt And Ici Synergism: Schedule Ici Partnementioning

confidence: 99%

Enhance the Immune Checkpoint Inhibitors Efficacy with Radiotherapy Induced Immunogenic Cell Death: A Comprehensive Review and Latest Developments

Procureur

Simonaggio

Bibault

et al. 2021

Cancers

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The immunogenic cell death (ICD) is defined as a regulated cell death able to induce an adaptive immunity. It depends on different parameters including sufficient antigenicity, adjuvanticity and favorable microenvironment conditions. Radiation therapy (RT), a pillar of modern cancer treatment, is being used in many tumor types in curative, (neo) adjuvant, as well as metastatic settings. The anti-tumor effects of RT have been traditionally attributed to the mitotic cell death resulting from the DNA damages triggered by the release of reactive oxygen species. Recent evidence suggests that RT may also exert its anti-tumor effect by recruiting tumor-specific immunity. RT is able to induce the release of tumor antigens, to act as an immune adjuvant and thus to synergize with the anti-tumor immunity. The advent of new efficient immunotherapeutic agents, such as immune checkpoint inhibitors (ICI), in multiple tumor types sheds new light on the opportunity of combining RT and ICI. Here, we will describe the biological and radiobiological rationale of the RT-induced ICD. We will then focus on the interest to combine RT and ICI, from bench to bedside, and summarize the clinical data existing with this combination. Finally, RT technical adaptations to optimize the ICD induction will be discussed.

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“…In fact, radiation doses exceeding 5 Gy per fraction can effectively and directly destroy tumor cells and render these cells' elements for in-situ vaccination (5,20,48). On the other hand, the conventional schedules are more likely to cause systemic lymphopenia which affects immunotherapy efficacy and associated with poor prognosis (49)(50)(51).…”

Section: Exploration Of the Dose And Fraction Size Of Radiotherapymentioning

confidence: 99%

“…However, multisite treatment undoubtedly increases the irradiated volume and adverse reactions. Treatment-related lymphopenia was associated with a less effective response to anti-PD-1/PD-L1 therapy and inferior survival (49,50,79). Therefore, it may be helpful to maintain the number and function of immune cells so that they can be recruited to initiate anti-tumor immune response.…”

Section: Exploration Of Appropriate Volume and Numbers Of Irradiated mentioning

confidence: 99%

Optimizing the Treatment Schedule of Radiotherapy Combined With Anti-PD-1/PD-L1 Immunotherapy in Metastatic Cancers

Kong

Zhao

et al. 2021

Front. Oncol.

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Immune checkpoint inhibitors (ICIs) targeting programmed cell death protein-1 (PD-1), and programmed cell death ligand-1 (PD-L1) have been approved for a variety of malignant tumors and are widely used to treat patients with metastatic disease. However, the efficacy of PD-1 inhibitors is limited due to tumor heterogeneity, high tumor burden, and “cold” tumor microenvironment. Radiotherapy can improve the anti-tumor effects of PD-1/PD-L1 inhibitors in various ways. As a new radiotherapy method, stereotactic body radiotherapy (SBRT) or hypofractionated radiotherapy (HFRT) provides higher doses per fraction to the target lesions, thus achieving immune activation effects and overcoming tumor resistance to anti-PD-1/PD-L1 treatment, which significantly improves the local and distant control of tumors. However, for different metastatic situations, radiotherapy plays different roles in the combination therapy. In oligometastatic status, radiotherapy can be used as a local radical treatment aiming to eliminate cancers in cooperation with systemic PD-1 inhibitors. In other circumstances, like bulky metastasis or multiple metastatic tumors, radiotherapy can be used as adjuvant to systemic immunotherapy. This review focuses on the underlying mechanisms and optimization strategies for the combination of radiotherapy and anti-PD-1/PD-L1 therapy in metastatic disease.

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Absolute Lymphocyte Count Predicts Abscopal Responses and Outcomes in Patients Receiving Combined Immunotherapy and Radiation Therapy: Analysis of 3 Phase 1/2 Trials

Cited by 78 publications

References 18 publications

Radiation Therapy and the In Situ Vaccination Approach

Radiation Therapy and the In Situ Vaccination Approach

Enhance the Immune Checkpoint Inhibitors Efficacy with Radiotherapy Induced Immunogenic Cell Death: A Comprehensive Review and Latest Developments

Optimizing the Treatment Schedule of Radiotherapy Combined With Anti-PD-1/PD-L1 Immunotherapy in Metastatic Cancers

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