Background: Inflammation is a recognized contributor to muscle wasting. Research in injury and myopathy suggests that interactions between the skeletal muscle and immune cells confer a pro-inflammatory environment that influences muscle loss through several mechanisms; however, this has not been explored in the cancer setting. This study investigated the local immune environment of the muscle by identifying the phenotype of immune cell populations in the muscle and their relationship to muscle mass in cancer patients. Methods: Intraoperative muscle biopsies were collected from cancer patients (n = 30, 91% gastrointestinal malignancies). Muscle mass was assessed histologically (muscle fiber cross-sectional area, CSA; μm²) and radiologically (lumbar skeletal muscle index, SMI; cm²/m² by computed tomography, CT). T cells (CD4 and CD8) and granulocytes/phagocytes (CD11b, CD14, and CD15) were assessed by immunohistochemistry. Microarray analysis was conducted in the muscle of a second cancer patient cohort. Results: T cells (CD3+), granulocytes/phagocytes (CD11b+), and CD3−CD4+ cells were identified. Muscle fiber CSA (μm²) was positively correlated (Spearman’s r = > 0.45; p = < 0.05) with the total number of T cells, CD4, and CD8 T cells and granulocytes/phagocytes. In addition, patients with the smallest SMI exhibited fewer CD8 T cells within their muscle. Consistent with this, further exploration with gene correlation analyses suggests that the presence of CD8 T cells is negatively associated (Pearson’s r = ≥ 0.5; p = <0.0001) with key genes within muscle catabolic pathways for signaling (ACVR2B), ubiquitin proteasome (FOXO4, TRIM63, FBXO32, MUL1, UBC, UBB, UBE2L3), and apoptosis/autophagy (CASP8, BECN1, ATG13, SIVA1). Conclusion: The skeletal muscle immune environment of cancer patients is comprised of immune cell populations from the adaptive and innate immunity. Correlations of T cells, granulocyte/phagocytes, and CD3−CD4+ cells with muscle mass measurements indicate a positive relationship between immune cell numbers and muscle mass status in cancer patients. Further exploration with gene correlation analyses suggests that the presence of CD8 T cells is negatively correlated with components of muscle catabolism.

Background: Low muscle radiodensity on computed tomography (CT) scan, indicative of myosteatosis, is commonly observed in cancer patients and can be associated with poor prognosis. Radiodensity is typically measured at the level of the third lumbar vertebra (L3). It is unknown whether features at L3 reflect a systemic state affecting peripheral muscle groups, whether images used at different levels can be used as a surrogate if L3 images are unavailable, and how radiodensity varies between cancer types.Methods: Core and extremity muscle radiodensities were measured in whole body CT images from melanoma patients to evaluate the anatomical distribution of muscle radiodensity measurements. Core muscle radiodensity was measured in 891 patients with different cancer types to study malignancy‐dependent patterns in muscle radiodensity.Results: Low muscle radiodensity at L3 (<30 Hounsfield Unit) was associated with a corresponding lower muscle radiodensity in all muscle groups evaluated (P < 0.001). However, muscle radiodensities were lowest in the core muscle groups compared with muscles in the extremities. Muscle radiodensities at T12 closely correlated with measurements taken at L3 (r = 0.920, P < 0.001), but the correlation was weaker with mid‐thigh measurements (r = 0.745, P < 0.001). The distribution of muscle radiodensities varied significantly with cancer type (P = 0.002).Conclusions: The uniform distribution of low muscle radiodensity in cancer patients supports the hypothesis that the underlying mechanism for myosteatosis is systemic in nature. The most reliable measurements of muscle radiodensity are taken using images of core muscles. Variations in muscle radiodensity associated with cancer exist, suggesting that cancer‐specific biological drivers are at play.