Immunotherapy in Advanced Non-small Cell Lung Cancer Patients: Ushering Chemotherapy Through the Checkpoint Inhibitors?

Abstract

New ways of exploiting the immune system for cancer treatment have been tested for decades with moderate outcomes. Based on previous immunotherapy knowledge, agents targeting immune checkpoints seem to be remarkably effective in a wide range of tumors. Immune checkpoint inhibitors in metastatic non-small cell lung cancer (NSCLC) provide longlasting responses in specific patients. Nevertheless, with overall response rates ≤ 20%, combinational protocols for various patient subgroups are needed. A good partner treatment to immunotherapy could be chemotherapy, as it successfully modulates the immune response either by controlling or enhancing the antitumor immune activity. Primary research provides promising results in metastatic NSCLC patients using this approach, but further large-scale trials are needed. The implementation of immunotherapy in nonmetastatic cases is also appealing. We review the potential clinical benefits of immunotherapy alone or in concert with chemotherapy in NSCLC.

Correlating tumor-infiltrating lymphocytes and lung cancer stem cells: a cross-sectional study

“…However, in our study, we reported no correlation between CSCs and CD4+ cells. We believe that these data reflect what has been previously described in the literature for solid tumors (27)(28)(29)(30)(31)(32)(33)(34)(35), defining additional roles for CD4+ T cells, some of which are independent of other lymphocytes, that influence and/or contribute to tumor immunity during carcinogenesis. Consequently, our findings may underline the dualistic role of CD4+ T cells in antitumor activity (33).…”

“…The CD8+/Treg ratio was also a potential predictor of response to immunotherapy in mouse models of pancreatic cancer (27), which further supports its potential as an important biomarker and even a driver of the response to immunotherapy. Recent clinical studies are encouraging, showing that immunotherapy for lung cancer alone or in combination with conventional treatments significantly improves patient outcomes (27). However, the exact immune cell composition in NSCLC is not clear, and the scientific community is focusing their attention on specific intratumoral cell compositions that are represented by TILs (24).…”

“…Specifically, LCSCs may also generate unexplored biological insights that may lead to innovative diagnostic strategies for NSCLC in the context of immunotherapy. The reason for this correlation would require deeper investigations and may apparently argue against studies demonstrating an association between high levels of TILs and improved recurrence-free survival in stage 1a NSCLC patients and a reduced likelihood of systemic recurrence (27)(28)(29). In addition, a higher frequency of TILs within large node-negative NSCLC correlates with a decreased risk of disease recurrence and improved diseasefree survival (30).…”

Co-inhibitor expression on tumor infiltrating and splenic lymphocytes after dual checkpoint inhibition in a microsatellite stable model of colorectal cancer

“…Immune modulating therapies have demonstrated tremendous efficacy for malignancies such as melanoma and non-small cell lung cancer 1 , 2 . On the other hand, colorectal cancer (CRC) seems to respond differently based on whether or not the tumor has deficient DNA mismatch repair mechanisms.…”

Interface of cancer stem cells and cancer immunity

“…However, this result seems to be contradictory to the previous reports. High concentration of TILs was reported to correlate with improved disease free survival and decreased risk of recurrence in lung cancer (6)(7)(8)(9), whereas cancer stem cell (CSC) is generally linked to tumor recurrence and metastasis (10,11). CD133 has been widely used as a CSC marker in NSCLC (12).…”