それにしても is an expression used in Japanese as an extension of にしても ‘even though’, or ‘even if’. This grammar pattern may be translated as ‘nevertheless’, or ‘even so’, and merely points out that despite what was said previously, the speaker’s primary opinion is the following statement.
In most cases, それにしても simply highlights that while the speaker accepts or acknowledges the previous statement as true, that is not all there is to be considered.
それにしても will primarily appear at the beginning of sentences, or directly after a comma.

• 彼女（かのじょ）は新人（しんじん）だから仕方（しかた）がないが、それにしても仕事（しごと）ができなさすぎる。
  She’s new so we can’t blame her, but even so, she is not good at her job at all.
• 田中（たなか）くんは遅（おく）れてくると言（い）っていたが、それにしてもくるのが遅（おそ）すぎる。
  Tnka-kun said he will be late, but even so, it’s taking him too long to come.
• 漢字（かんじ）を勉強（べんきょう）し始（はじ）めてから1年（ねん）になる。それにしても、まだ全然（ぜんぜん）漢字（かんじ）が読（よ）めない。
  It has been a year since I started studying kanji. Nevertheless, I still can't read kanji at all.

Due to それにしても being used when the speaker is already aware of or accepts the situation of (A), (B) will frequently highlight something that is above or beyond that expectation.

• 家（いえ）に来（き）たばかりのときなんかお手（て）もできなかったのにね。それにしても、大（おお）きくなったね。
  When she first came to our house, he couldn't even give me his paw. Nevertheless, he got so big, don’t you think?
• 先輩（せんぱい）、昨日（きのう）はご馳走様（ちそうさま）でした！それにしても、あそこの料理（りょうり）は最高（さいこう）でしたね！
  Senpai, thank you for treating me yesterday! Nevertheless, that restaurant was awesome, wasn’t it?!