Unraveling the triad of immunotherapy, tumor microenvironment, and skeletal muscle biomechanics in oncology

Abstract

The intricate interaction between skeletal muscle biomechanics, the tumor microenvironment, and immunotherapy constitutes a pivotal research focus oncology. This work provides a comprehensive review of methodologies for evaluating skeletal muscle biomechanics, including handheld dynamometry, advanced imaging techniques, electrical impedance myography, elastography, and single-fiber experiments to assess muscle quality and performance. Furthermore, it elucidates the mechanisms, applications, and limitations of various immunotherapy modalities, including immune checkpoint inhibitors, adoptive cell therapy, cancer vaccines, and combined chemoimmunotherapy, while examining their effects on skeletal muscle function and systemic immune responses. Key findings indicate that although immunotherapy is effective in augmenting antitumor immunity, it frequently induces muscle-related adverse effects such as weakness, fatigue, or damage, primarily mediated by cytokine release and immune activation. This work underscores the significance of immune niches within the tumor microenvironment in influencing treatment outcomes and proposes strategies to optimize therapy through personalized regimens and combinatorial approaches. This review highlights the need for further research on the formation of immune niches and interactions muscle-tumor. Our work is crucial for advancing the efficacy of immunotherapy, reducing adverse effects, and ultimately improving survival rates and quality of life of patients with cancer.

Keywords: immune checkpoint inhibitors; immune niches; immunotherapy; skeletal muscle biomechanics; tumor microenvironment.

Figure 1

Interactions between immune cells and tumor cells in the tumor microenvironment.

Figure 2

Cytokine storm and its clinical manifestations.

Figure 3

Diagram of percutaneous muscle biopsy experiment. (A) Image of the permeabilized fiber connected to a force transducer and servo motor. (B) Relaxation testing of the activation solution. (C) Duration of unloading after the peak force was achieved. (D) Unloaded shortening velocity. (E) Force response of vastus lateralis fibers exposed to DTT and DTDP-GSH. (F) Phases experienced by isometrically activated fibers during rapid length release. (G) Bland-Altman plot showing thigh muscle mass determined by MRI on the x-axis. (H) Isotonic contraction experiments, measuring force-velocity relationship. (I) Shortening velocity after fiber unloading. (J) Strain ultrasound elastography of the supraspinatus tendon (a), infraspinatus tendon, and posterior capsule (b).

Figure 4

(A) Illustration of data generation in A- and B-mode ultrasound imaging. (B) Longitudinal B-mode ultrasound image of the medial gastrocnemius muscle of a healthy volunteer. (C) Diagram of strain ultrasound techniques, including freehand cyclic compression (a), internal organ pulsation from the heart and lungs (b), acoustic radiation force impulse (c), and external source vibration (d). (D) Schematic of shear-wave elastography techniques, including external mechanism vibration (a), single-point focused acoustic radiation force impulse (b), and multi-point focused acoustic radiation force impulse (c).

Figure 5

Principles and interrelationships of various cancer treatment strategies. (A) immune checkpoint inhibitor therapy. (B) Chimeric Antigen Receptor T-Cell (CAR-T) therapy. (C) Cancer Vaccine Therapy. (D) Combined Chemotherapy and Immunotherapy.