5.2.3. Specific Tumour Antibodies

In the tumour of some malignant neoplasms, B cells are found, organised in germinal centers, which results in the presence of plasma cells. Their function is not yet known, but it is assumed that they are involved in a constant immune reaction at the site of the tumour. In cancer patients, circular antigen-specific auto-antibodies (AAbs) derived from tumour can be detected, which helps to determine immunogenic targets.

Ultimately, cancer sera contain antibodies that react against autologous cell antigens, AATs. Auto-antibodies associated with a particular type of cancer target these abnormal cellular proteins that are involved in tumour transformation, so autoantibodies can be considered as reporters that identify aberrant cellular mechanisms in tumorigenesis [300]. By examining the sera of cancer patients, new TAAs can be identified, such as p62 and p90 [301,302], which have already been identified with this approach. The sensitivity and specificity of different antigen-antibody systems as markers in cancer can also be evaluated to develop TAAs array systems for diagnosis, prediction, and follow-up in cancer patients [300].

The detection of tumour-associated target-specific IgG could act as a substitute for the presence of T cells [294]. It is difficult for these auto-antibodies to have a direct antitumour role, as most of the antigens they target are intracellular [303]. In the example of checkpoint inhibitors, the presence of NY-ESO-1 specific autoantibodies are known to be associated with increased clinical benefit in patients with advanced melanoma who are treated with ipilimumab [299]. This suggests that tumour-specific antibodies may be an indicator of the presence of tumour-specific T cells in the tumour microenvironment and patients with pre-existing ability to react to tumours would be favourably disposed to immunomodulatory therapy [294].

The presence of tertiary lymphoid structures, consisting of germ-center-organised B cells, plasma cells, and T cells, is highly predictive of progression-free survival and overall survival in solid tumours such as melanoma and NSCLC [304,305]. These structures are close to the tumour tissue, so they are believed to play an important role in local immunogenicity and infiltrating B and T cells are known to have tumour specificity. When B cells isolated from NSCLC tumours differentiate in vitro to plasma cells, they produce antibodies to tumour-associated antigens such as NY-ESO-1, TP53, or XAGE-1 [305]. Therefore, these tumour antigen-specific B cells participate in immune mechanisms and are potential targets for the application of immunotherapy. Associating the presence of local antibodies with systemic humoral immunity will be key to establishing serology as a prognostic or predictive marker [294].

For patients with breast cancer who present difficult to interpret mammography, Provista Diagnostics has developed a kit called Videssa ® Breast that, through a blood extraction, allows a more accurate and improved diagnosis, avoiding unnecessary biopsies. It is based on proteomic technology to analyse multiple biomarkers of serum tumour proteins and tumour-associated auto-antibodies (TAAbs) associated with cancer. This kit incorporates nine serum proteins as biomarkers and 20 TAAbs. It allows detecting the presence or absence of breast cancer in women between 25 and 75 years old, with a sensitivity of 93.3% and a specificity of 63.8%. If this test is combined with image diagnosis, 100% of breast cancers can be detected. In all trials performed so far, all breast cancers were identified at an early stage [306]. This demonstrates the importance of detecting specific AAbs for TAAs to improve the diagnosis of patients with cancer.
