Skeletal muscle cells actively shape (auto)immune responses

Afzali, Ali Maisam; Müntefering, Thomas; Wiendl, Heinz; Meuth, Sven G.; Ruck, Tobias

doi:10.1016/j.autrev.2017.12.005

Cited by 79 publications

(63 citation statements)

References 140 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Some authors have already speculated about the negative influence that alterations in body composition of sarcopenic patients could have on declining immunity . A recent article further clarified that skeletal muscle cells actively modulate immune response in health and disease, particularly autoimmune diseases . Indeed, they interact with immune cells like non‐professional antigen presenting cells, expressing major histocompatibility complexes I and II and affecting T cell function …”

Section: Discussionmentioning

confidence: 99%

“…10 A recent article further clarified that skeletal muscle cells actively modulate immune response in health and disease, particularly autoimmune diseases. 11 Indeed, they interact with immune cells like non-professional antigen presenting cells, expressing major histocompatibility complexes I and II and affecting T cell function. 11 Moreover, skeletal muscle tissue could be an important IL-15 producer, which is necessary for natural killer (NK) cell function and homeostasis.…”

Section: Discussionmentioning

confidence: 99%

“…11 Indeed, they interact with immune cells like non-professional antigen presenting cells, expressing major histocompatibility complexes I and II and affecting T cell function. 11 Moreover, skeletal muscle tissue could be an important IL-15 producer, which is necessary for natural killer (NK) cell function and homeostasis. 12 When muscle wasting is combined with elevated inflammatory cytokines (as occurs in cancer patients), we presume that it affects NK cell numbers and survival.…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Predictive value of skeletal muscle mass for immunotherapy with nivolumab in non‐small cell lung cancer patients: A “hypothesis‐generator” preliminary report

et al. 2019

View full text Add to dashboard Cite

Sarcopenia represents one of the hallmarks of all chronic disease, including non‐small cell lung cancer (NSCLC). A computed tomography scan is an easy modality to estimate the skeletal muscle mass through cross‐sectional image analysis at the level of the third lumbar vertebra (L3). Baseline skeletal muscle mass (SMM) was evaluated using gender‐specific cutoffs for skeletal muscle index in NSCLC patients administered immunotherapy with nivolumab to evaluate its possible correlations with clinical outcomes. From April 2015 to August 2018, 23 stage IV NSCLC patients were eligible for image analysis. Nine patients (39.1%) had low SMM. Among patients with baseline low and non‐low SMM, median progression free survival was 3.1 and 3.8 months, respectively (P = 0.0560), while median overall survival was 4.1 and 13 months, respectively (P = 0.2866). This hypothesis‐generating preliminary report offers the opportunity to speculate about the negative influence of sarcopenia on immune response. In our opinion, nutritional status could affect the clinical outcomes of immunotherapy, even if we cannot make definitive conclusions here. Further studies on the topic are required.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Predictive value of skeletal muscle mass for immunotherapy with nivolumab in non‐small cell lung cancer patients: A “hypothesis‐generator” preliminary report

et al. 2019

View full text Add to dashboard Cite

show abstract

“…Glycosylation changes in muscle-associated human disease have focused in muscular dystrophies ( 86 ) and congenital disorders of glycosylation ( 87 ). Recent studies have shown that muscle cell surface glycosylation is finely regulated and subjected to alterations under inflammatory conditions ( 88 ), pointing to a possible interaction between muscle glycocalyx and the extracellular milieu, which is particularly enriched in immune cells and antibodies in IIM patients ( 89 ).…”

Section: Glycans As Modulators Of Hyper-reactive/autoimmune Responsesmentioning

confidence: 99%

Glycans as Key Checkpoints of T Cell Activity and Function

et al. 2018

View full text Add to dashboard Cite

The immune system is highly controlled and fine-tuned by glycosylation, through the addition of a diversity of carbohydrates structures (glycans) to virtually all immune cell receptors. Despite a relative backlog in understanding the importance of glycans in the immune system, due to its inherent complexity, remarkable findings have been highlighting the essential contributions of glycosylation in the regulation of both innate and adaptive immune responses with important implications in the pathogenesis of major diseases such as autoimmunity and cancer. Glycans are implicated in fundamental cellular and molecular processes that regulate both stimulatory and inhibitory immune pathways. Besides being actively involved in pathogen recognition through interaction with glycan-binding proteins (such as C-type lectins), glycans have been also shown to regulate key pathophysiological steps within T cell biology such as T cell development and thymocyte selection; T cell activity and signaling as well as T cell differentiation and proliferation. These effects of glycans in T cells functions highlight their importance as determinants of either self-tolerance or T cell hyper-responsiveness which ultimately might be implicated in the creation of tolerogenic pathways in cancer or loss of immunological tolerance in autoimmunity. This review discusses how specific glycans (with a focus on N-linked glycans) act as regulators of T cell biology and their implications in disease.

show abstract

“…Considering that a negative influence of body composition alterations and sarcopenia on declining immunity has already been assumed 4 , it is becoming clearer that after the advent of immune checkpoint inhibitors (ICIs), the body composition evaluation could regain importance. For example, skeletal muscle cells might modulate immune response in health and disease (autoimmune diseases particularly) 5 , interacting with immune cells like non-professional antigen presenting cells (APCs), and expressing major histocompatibility complexes I and II 5 . It is been already reported that sarcopenic melanoma patients are more likely to experience immune related adverse events (irAEs) 6,7 .…”

mentioning

confidence: 99%

Weighing the role of skeletal muscle mass and muscle density in cancer patients receiving PD-1/PD-L1 checkpoint inhibitors: a multicenter real-life study

Cortellini

Bozzetti

Palumbo

et al. 2020

Sci Rep

View full text Add to dashboard Cite

Sarcopenia represents one of the hallmarks of all chronic diseases, including cancer, and was already investigated as a prognostic marker in the pre-immunotherapy era. Sarcopenia can be evaluated using cross-sectional image analysis of CT-scans, at the level of the third lumbar vertebra (L3), to estimate the skeletal muscle index (SMI), a surrogate of skeletal muscle mass, and to evaluate the skeletal muscle density (SMD). We performed a retrospective analysis of consecutive advanced cancer patient treated with PD-1/PD-L1 checkpoint inhibitors. Baseline SMI and SMD were evaluated and optimal cut-offs for survival, according to sex and BMI (+/−25) were computed. The evaluated clinical outcomes were: objective response rate (ORR), immune-related adverse events (irAEs), progression free survival (PFS) and overall survival (OS). From April 2015 to April 2019, 100 consecutive advanced cancer patients were evaluated. 50 (50%) patients had a baseline low SMI, while 51 (51%) had a baseline low SMD according to the established cut offs. We found a significant association between SMI and ECOG-PS (p = 0.0324), while no correlations were found regarding SMD and baseline clinical factors. The median follow-up was 20.3 months. Patients with low SMI had a significantly shorter PFS (HR = 1.66 [95% CI: 1.05-2.61]; p = 0.0291) at univariate analysis, but not at the multivariate analysis. They also had a significantly shorter OS (HR = 2.19 [95% CI: 1.31-3.64]; p = 0.0026). The multivariate analysis confirmed baseline SMI as an independent predictor for OS (HR = 2.19 [1.31-3.67]; p = 0.0027). We did not find significant relationships between baseline SMD and clinical outcomes, nor between ORR, irAEs and baseline SMI (data not shown). Low SMI is associated with shortened survival in advanced cancer patients treated with PD1/PDL1 checkpoint inhibitors. However, the lack of an association between SMI and clinical response suggests that sarcopenia may be generally prognostic in this setting rather than specifically predictive of response to immunotherapy.Sarcopenia is the condition of loss of muscle mass, with decreased muscle power, and it is one of the hallmarks of cancer, which negatively affects the most of clinical outcomes such as toxicities and survival 1 . The interactions must recognize also the lack of other adiposity metrics, such as the waist circumference, the waist-to-height ratio, and the body fat percentage. Moreover, the CT imaging analysis was limited by the data availability; indeed, the acquisition protocol was planned according to the presence of previous examination. conclusionOur finding of a significant shorter OS for low-SMI patients treated with PD-1/PD-L1 checkpoint inhibitors, suggests that sarcopenia might have a prognostic role, rather than predictive. However, to properly weighing our results, we must consider the significant association between poorer PS and low-SMI. Without making conclusive considerations, we can assume that after the advent of ICIs, we should give back further relevance to baseline nut...

show abstract

Skeletal muscle cells actively shape (auto)immune responses

Cited by 79 publications

References 140 publications

Predictive value of skeletal muscle mass for immunotherapy with nivolumab in non‐small cell lung cancer patients: A “hypothesis‐generator” preliminary report

Predictive value of skeletal muscle mass for immunotherapy with nivolumab in non‐small cell lung cancer patients: A “hypothesis‐generator” preliminary report

Glycans as Key Checkpoints of T Cell Activity and Function

Weighing the role of skeletal muscle mass and muscle density in cancer patients receiving PD-1/PD-L1 checkpoint inhibitors: a multicenter real-life study

Contact Info

Product

Resources

About