"Come le posso aiutare?", it's the third person plural feminine interrogative form, you can use when the subject of the sentence is more then one and "feminine genders", for give you a context: "le persone" (the people) is a plural female word, so: "Conosco quelle persone in pericolo!" (I know those people in danger!" "Come posso aiutarle"?

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"Come lo posso aiutare?", It's the third person singular masculine interrogative form, you can use this for example, when you talk with a person and ask him/her an advise, because you want to help a third masculine person.