Longitudinal analysis of lung cancer-specific immunity in stage III and IV non-small cell lung cancer patients.

There is evidence that tumor-specific T cell responses can contribute to the control of lung carcinoma. However, there is little known about the longitudinal development of non-small cell lung carcinoma-specific T cell responses both in peripheral blood and at the tumor site is likely to offer leads for early monitoring of treatment response and for the development of more targeted immunotherapies. Furthermore, it has been postulated that also other therapeutic strategies that have veen developed or are currently used in NSCLC potentially exert their effect in part through the induction of a lung carcinoma-specific T cell response. In this concept chemotherapy or targeted therapy micht act to 'prime'the immune response, whereas immune checkpoint blockade such as anti-CTLA-4 or anti PD1 acts to 'boost' it by augmenting the immune response. At present, no data are available on the relationschip between treatment of lung carcinoma with these types of drugs and teh development of tumor-specific T cell responses, either in peripheral blood or at the tumor site.

1. To study the effect of treatment modalities immunotherapy (anti-PD1 or anti-PDL-1), and targeted therapy (crizotinib, gefitinib, or erlotinib) on the size and diversity of lung carcinoma-specific T cell populations as measured by immune assays, including MHC tetramer technology and antigen-specific cytokine production;

2. To examine effect of the treatment modalities immunotherapy (e.g. anti-PD1, anti-PDL-1), and targeted therapy (e.g. crizotinib, gefitinib) on the immune infiltrates present within biopsies;

3. To examine the repertoire of potential T cell antigens in NSCLC lesions by genomic analysis.

Blood sampling will be done prior start of treatment (50ml), at the moment of first response evaluation (100ml), followed by 3 monthly sampling (50ml) , ≤ 3 drawings in total.

From patients who receive this type of treatments, a biopsy (optional) will be taken prior start of treatment, 1-2 weeks after start of treatment and at the time of proven disease progression, in order to study the presence of new genetic mutations that lead to resistance to these targeted agents.

Tumorbiopsies and peripheral blood samples.