Adversaries may communicate using OSI application layer protocols to avoid detection/network filtering by blending in with existing traffic. Commands to the remote system, and often the results of those commands, will be embedded within the protocol traffic between the client and server. 

Adversaries may utilize many different protocols, including those used for web browsing, transferring files, electronic mail, or DNS. For connections that occur internally within an enclave (such as those between a proxy or pivot node and other nodes), commonly used protocols are SMB, SSH, or RDP.(Citation: Mandiant APT29 Eye Spy Email Nov 22) 
Application Layer Protocol
source_name: mitre-attack  url: https://attack.mitre.org/techniques/T1071  external_id: T1071     source_name: University of Birmingham C2  description: Gardiner, J.,  Cova, M., Nagaraja, S. (2014, February). Command & Control Understanding, Denying and Detecting. Retrieved April 20, 2016.  url: https://arxiv.org/ftp/arxiv/papers/1408/1408.1136.pdf     source_name: Mandiant APT29 Eye Spy Email Nov 22  description: Mandiant. (2022, May 2). UNC3524: Eye Spy on Your Email. Retrieved August 17, 2023.  url: https://www.mandiant.com/resources/blog/unc3524-eye-spy-email     