Stereotactic Ablative Radiation Therapy in 3 Fractions Induces a Favorable Systemic Immune Cell Profiling in Prostate Cancer Patients

Palermo, Belinda; Bottero, Marta Carla; Panetta, Mariangela; Faiella, A.; Sperduti, Isabella; Masi, Sara De; Frisullo, Giuseppe; Foddai, Maria Laura; Cordone, Iole; Nisticò, Paola; Sanguineti, Giuseppe

doi:10.1080/2162402x.2023.2174721

Cited by 8 publications

(5 citation statements)

References 43 publications

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“…Consistent with this concept, a study on early-stage NSCLC patients demonstrated that the proliferation of circulating CD8 + T cells was increased by SBRT with a daily dose of 10 Gy or less but not with higher doses [37]. Nonetheless, an analysis of prostate cancer patients and metastatic breast cancer patients did not observe any difference among varying daily doses [44,72], suggesting that the relationship between CD8 + T cell responses and the daily dose should be investigated in detail.…”

Section: Factors That Influence Rt-induced Cd8 + T Cell-responsesmentioning

confidence: 90%

“…Similarly, another study showed that circulating CD8 + T cells reactive to tumor-associated antigens were increased in two prostate cancer patients at 1 month after RT [43]. Palermo et al compared the effects of varying RT schemes, including SBRT, hypofractionated RT, and conventionally fractionated RT, and revealed that the proportion of CD8 + T cells among circulating T cells was increased after RT regardless of the RT scheme [44]. Notably, effector memory CD8 + T cells and VISTA-expressing CD8 + T cells were increased only in patients undergoing SBRT.…”

Section: Changes In Cd8 + T Cells Following Rtmentioning

confidence: 99%

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Modulation of CD8+ T Cell Responses by Radiotherapy—Current Evidence and Rationale for Combination with Immune Checkpoint Inhibitors

Jeon,

Song,

Eom

et al. 2023

IJMS

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Radiotherapy for cancer has been known to affect the responses of immune cells, especially those of CD8+ T cells that play a pivotal role in anti-tumor immunity. Clinical success of immune checkpoint inhibitors led to an increasing interest in the ability of radiation to modulate CD8+ T cell responses. Recent studies that carefully analyzed CD8+ T cell responses following radiotherapy suggest the beneficial roles of radiotherapy on anti-tumor immunity. In addition, numerous clinical trials to evaluate the efficacy of combining radiotherapy with immune checkpoint inhibitors are currently undergoing. In this review, we summarize the current status of knowledge regarding the changes in CD8+ T cells following radiotherapy from various preclinical and clinical studies. Furthermore, key biological mechanisms that underlie such modulation, including both direct and indirect effects, are described. Lastly, we discuss the current evidence and essential considerations for harnessing radiotherapy as a combination partner for immune checkpoint inhibitors.

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Section: Factors That Influence Rt-induced Cd8 + T Cell-responsesmentioning

confidence: 90%

Section: Changes In Cd8 + T Cells Following Rtmentioning

confidence: 99%

Modulation of CD8+ T Cell Responses by Radiotherapy—Current Evidence and Rationale for Combination with Immune Checkpoint Inhibitors

Jeon,

Song,

Eom

et al. 2023

IJMS

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“…The results showed that conventional radiotherapy has a negative impact on systemic immunity, resulting in an increase in neutrophils/lymphocytes and a decrease in total lymphocyte count. In contrast, SBRT increased B cell, central memory T cell, and effector CD8 + T cell infiltration in the TME, as well as increased CD8/Treg ratio (29). In summary, SBRT could activate the immune system through multiple pathways and create an ideal TME for subsequent immunotherapy (Figure 1).…”

Section: The Interplay Between Sbrt and Antitumour Immune Responsementioning

confidence: 99%

“…For example, the analysis of paired lung cancer samples following SBRT revealed an increase in the diversity of the T cell receptor repertoire and programmed cell death ligand 1 (PD-L1) expression, while no significant increase of CD8 + T cell and IFN expression was observed within tumour tissues (33). In addition to PD-L1, SBRT can also significantly up-regulate V-domain immunoglobulin suppressor of T cell activation (VISTA) expression in CD8 + T cells (29). It is worth noting that not all immune checkpoints are elevated following SBRT.…”

Section: The Interplay Between Sbrt and Antitumour Immune Responsementioning

confidence: 99%

Neoadjuvant SBRT combined with immunotherapy in NSCLC: from mechanisms to therapy

Shi

et al. 2023

Front. Immunol.

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The utilisation of neoadjuvant immunotherapy has demonstrated promising preliminary clinical outcomes for early-stage resectable non-small-cell lung cancer (NSCLC). Nevertheless, it is imperative to develop novel neoadjuvant combination therapy regimens incorporating immunotherapy to further enhance the proportion of patients who derive benefit. Recent studies have revealed that stereotactic body radiotherapy (SBRT) not only induces direct tumour cell death but also stimulates local and systemic antitumour immune responses. Numerous clinical trials have incorporated SBRT into immunotherapy for advanced NSCLC, revealing that this combination therapy effectively inhibits local tumour growth while simultaneously activating systemic antitumour immune responses. Consequently, the integration of SBRT with neoadjuvant immunotherapy has emerged as a promising strategy for treating resectable NSCLC, as it can enhance the systemic immune response to eradicate micrometastases and recurrent foci post-resection. This review aims to elucidate the potential mechanism of combination of SBRT and immunotherapy followed by surgery and identify optimal clinical treatment strategies. Initially, we delineate the interplay between SBRT and the local tumour immune microenvironment, as well as the systemic antitumour immune response. We subsequently introduce the preclinical foundation and preliminary clinical trials of neoadjuvant SBRT combined with immunotherapy for treating resectable NSCLC. Finally, we discussed the optimal dosage, schedule, and biomarkers for neoadjuvant combination therapy in its clinical application. In conclusion, the elucidation of potential mechanism of neoadjuvant SBRT combined immunotherapy not only offers a theoretical basis for ongoing clinical trials but also contributes to determining the most efficacious therapy scheme for future clinical application.

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“…Immune monitoring of the 18 patients showed that RT can affect the balance of systemic immune cells, with the main differences observed between SBRT and conventionally fractionated RT [106]. While conventional RT had a long-term negative effect on the sys-temic immune profile, SBRT favorably impacts immune response in terms of increased B cells, central-memory and effector-memory CD8 + T cells, along with decreased Treg cells after treatment.…”

Section: Complicationsmentioning

confidence: 99%

Review of Current Treatment Intensification Strategies for Prostate Cancer Patients

Wasim,

Park,

Nam

et al. 2023

Cancers

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Prostate cancer (PCa) used to be one of the most common nondermatologic cancers in men that can be treated only with surgery. However, a revolutionary breakthrough came in the 1980s with the introduction of long-acting luteinizing hormone-releasing hormone (LHRH) agonists for the curative treatment of PCa. This paradigm shift contributed to the combined use of androgen deprivation therapy (ADT), chemotherapy, and radiotherapy for the treatment. The latest data highlight the use of treatment intensification (TI), i.e., combined use of radiotherapy (RT) and hormonal or drug treatments, for localized or locally advanced PCa. Indeed, the results of combined modality treatments have shown a reduction in disease-specific mortality and improved overall survival. Although TI seems promising, more research studies are warranted to confirm its efficacy. This review summarizes the latest available outcome results of pivotal trials and clinical studies on the efficacy of TI.

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Stereotactic Ablative Radiation Therapy in 3 Fractions Induces a Favorable Systemic Immune Cell Profiling in Prostate Cancer Patients

Cited by 8 publications

References 43 publications

Modulation of CD8+ T Cell Responses by Radiotherapy—Current Evidence and Rationale for Combination with Immune Checkpoint Inhibitors

Modulation of CD8+ T Cell Responses by Radiotherapy—Current Evidence and Rationale for Combination with Immune Checkpoint Inhibitors

Neoadjuvant SBRT combined with immunotherapy in NSCLC: from mechanisms to therapy

Review of Current Treatment Intensification Strategies for Prostate Cancer Patients

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