Immunoglobulin G and Subclasses as Potential Biomarkers in Metastatic Melanoma Patients Starting Checkpoint Inhibitor Treatment

J Immunother. 2019 Apr;42(3):89-93. doi: 10.1097/CJI.0000000000000255.


Checkpoint inhibitors have improved survival of metastatic melanoma. However, reliable biomarkers to predict response are still needed. Immunoglobulin G (IgG) antibody subclasses reflect immunocompetence in individuals and are known to be involved in essential functions in our immune system. This prospective study evaluated the association between serum IgG with its subclasses IgG1, IgG2, IgG3, and IgG4 and antitumor response according to RECIST 1.1. Serum samples from 49 patients were prospectively collected before the start of treatment with a checkpoint inhibitor. We observed a statistically significant association of baseline IgG2 with response to therapy (P=0.011). After defining optimal cutpoints, we found significant associations between total IgG (>9.66 g/L, P=0.038), IgG1 (>6.22 g/L, P=0.025), IgG2 (>2.42 g/L, P=0.019), and IgG3 (>0.21 g/L, P=0.034) with progression-free survival. Prolonged overall survival was associated with elevated IgG2 (>2.42 g/L, P=0.043). Together, these findings define total IgG and subclasses as predictors of clinical successful checkpoint inhibition in metastatic melanoma patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents, Immunological / therapeutic use*
  • Biomarkers, Tumor / blood*
  • CTLA-4 Antigen / antagonists & inhibitors
  • Female
  • Humans
  • Immunoglobulin G / blood*
  • Immunotherapy / methods*
  • Male
  • Melanoma / drug therapy*
  • Melanoma / mortality
  • Middle Aged
  • Neoplasm Metastasis
  • Patient Selection
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors
  • Prospective Studies
  • Survival Analysis


  • Antineoplastic Agents, Immunological
  • Biomarkers, Tumor
  • CTLA-4 Antigen
  • CTLA4 protein, human
  • Immunoglobulin G
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor