Manage Unsubscribes 

When you go to send your email using a data extension, make sure you use a publication list. Once you send your email with your combo of data extension and publication list, anyone who unsubscribes will have their unsubscribe stored on the publication list you used. When you go to send an email on the same topic or theme again, the publication list will automatically stop emails from being sent to the people who have previously unsubscribed. 

If someone replies to your email asking to unsubscribe, you have two options: tell them to click the unsubscribe link in their original email, or you can do that for them. The link to unsubscribe in their email is paired with their record in the publication list, so it doesn't matter who clicks it.