Nowadays immunotherapy is considered the tip of the arrow as treatment for non-small cell lung cancer for inoperable patients. Programmed death-ligand 1 is considered a valuable marker for the success of immunotherapy. The higher the score ≥50% the more successful the treatment will be. However; previous studies have presented favorable data even for those patients where the programmed death-ligand 1 was ≤50% or even 0%, therefore it can be administered as first line treatment in these patients with the addition of chemotherapy or radiotherapy. Other treatment modalities are tested as surrogates like gene therapy with immunotherapy to improve the results in patients with programmed death-ligand 1 was ≤50% or even 0%. The main issue for these patients is an adverse effect pneumonitis, in case we will present the valuable method of lung parenchyma sampling with cryobiopsy for early diagnosis of immunotherapy induced pneumonitis.